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Abstracts
This article was originally published by Wolters Kluwer - Medknow and was migrated to Scientific Scholar after the change of Publisher.
Category: Cardiology
Cardio 1: Myocardial infarction in non-obstructive coronary arteries – Where does myocardial perfusion imaging stand?
Ramya S, Neeraj Kumar, A. V. S. Anil Kumar, I. P. Dubey, M. G. Vishnoi, J. S. Arora, Archana Yadav, Nithya Anandaraman
Department of Nuclear Medicine, Army Hospital Research and Referral, New Delhi, India
Introduction: Myocardial infarction with non obstructive coronary arteries is defined as acute myocardial infarction (AMI) with angiographically non obstructive coronary artery disease or stenosis ≤50%. MINOCA is reported in 6–15% of patients with AMI and is generally observed in relatively young patients with lower prevalence of traditional cardiovascular risk factors. MINOCA is a heterogeneous group of conditions that include both atherosclerotic (coronary plaque disruption) and non-atherosclerotic (spontaneous coronary artery dissection, coronary artery spasm, coronary artery embolism, coronary microvascular dysfunction, and supply–demand mismatch) causes resulting in myocardial damage that is not due to obstructive coronary artery disease. Cardiac magnetic resonance (CMR) is the gold standard for diagnosis of MINOCA. Materials and Methods: This is case series of diagnosed cases of MINOCA with cardiac myocardial perfusion imaging. Patient preparation, radioactivity and stress protocol were followed as per standard guidelines. Single photon emission computed tomography (SPECT) images were acquired with a 2-detector gamma camera with SPECT (ECAM SCINTRON). Filtered back-projection (FBP) with a Butterworth filter (order 5, cut off frequency 0.45)/iterative reconstruction will be used for tomographic reconstruction with no attenuation/ scatter correction. Automated quantification of SPECT-MPI using quantitative perfusion software (Cedars Sinai, Los Angeles, California or Corridor 4DM, MiE) was performed. Results: Out of 3 patients who are in mid 40s, 1 male and 2 female, the two patients had normal angiographic findings. The first patient showed normal perfusion imaging with normal wall thickening and contractility. The second patient showed mild hypoperfusion in apical anterior segment of myocardium, normal motion and wall thickening. The third patient showed normal epicardial coronaries with TIMI II flow in coronary angiography. His perfusion imaging revealed mild reversible perfusion defect in apical anterior segment with normal motion and contractility. All the three patients had non obstructive coronary angiography and still 2 out of 3 showed mild hypoperfusion in MPI. Conclusion: The present case series suggests that myocardial perfusion imaging plays crucial role in early diagnosis of MINOCA. Further more similar studies in larger population could help in delineating the role of MPI in definitive diagnosis and follow up of the patients.
Cardio 2: Comparison of LVEF assessed by conventional gated blood pool SPECT (NaI(Tl)), CZT-planar and CZT-SPECT with planar (NaI(Tl)) using radionuclide ventriculography
S. Chaudhary, H. Singh, A. Kumar, B. R. Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: Estimation of left ventricular ejection fraction (LVEF) using equilibrium radionuclide ventriculography is an established method for assessment of left ventricular function. Earlier planar MUGA was considered most accurate for LVEF calculation but its accuracy limits in assessment of ventricular function due to overlapping atrium, low counts, high background leading to poor demarcation of ventricle and 2-dimensional mode of imaging. This problem was resolved by tomographic imaging technology ECG gated blood pool SPECT study. Moreover, CZT detector-based cameras have higher image resolution, better counting statistics, faster recording speed, and/or enable a reduction of the patient radiation dose. This study has been designed to assess the correlation between the LVEF measured by conventional NaI(Tl) detector-based SPECT, dedicated cardiac CZT detector based planar and SPECT with planar MUGA. Materials and Methods: The study consisted of 22 patients, 11:11; F:M, age = 17-72 years, who were referred to our department for assessment of left ventricular function using radionuclide ventriculography. The patients were acquired on both Philips Brightview XCT Cardiac Camera (SPECT/CT) Netherland and D-SPECT Cardio from Dynamic Spectrum Israel after in vivo labeling of RBCs with 99mTc. The planar images on gamma camera were acquired on the best septal view for 800 beats or 6 million counts. Then the SPECT images were acquired as per standard protocol. In D-SPECT system, the patient was positioned in supine position and ROI was drawn on left ventricular cavity. First, SPECT images of patient were acquired, and then planar images were acquired in the in-built software planar MUGA provided by company. For statistical analysis the normality of data was checked using Shapiro-Wilk test, and Pearson's coefficient of correlation (r) was calculated for the different sets of values with significance level kept at p-value less than 0.05. Bland–Altman plots were inspected to visually assess the between-agreement measurements from different methods. Linear regression analysis was done to look for proportional bias between the LVEF results. Results: The data was normally distributed (in all cases p-value was >0.05). The mean ± SD LVEF values of conventional SPECT, CZT-Planar, CZT-SPECT and Planar MUGA (NaI(Tl)) were 50.18 ± 15.34, 49.14 ± 14.57, 49.91 ± 14.97 and 45.59 ± 15.50 respectively. LVEF calculated from by various methods showed good correlation with NaI(Tl)-Planar as follows: NaI(Tl)-SPECT, r = 0.950 p < 0.001; CZT-SPECT, r = 0.929 p <0.001; and CZT-Planar, r = 0.971 p < 0.001. Bland-Altman plot showed good agreement between NaI(Tl)-Planar and other three methods. On linear regression analysis p-value was >0.05 which is indicative of the absence of any statistically significant proportional bias between results. Conclusion: This study showed good correlation and agreement between NaI(Tl)- Planar to NaI-(Tl)-SPECT and both CZT-Planar and CZT-SPECT. Because of the excellent temporal, spatial, and energy resolution of CZT based D-SPECT can substitute the planar ERNA with advantage of having shorter acquisition time and better image quality. Also, the radiation dose to patient can be minimized.
Cardio 3: TC-99M PYP scintigraphy as a noninvasive diagnostic tool for determining attr cardiac amyloidosis
M. Jayesh, Indirani Muthukrishnan, Shelley Simon
Department of Nuclear Medicine, Apollo Hospitals, Chennai, Tamil Nadu, India
Introduction: Deposition of misfolded proteins, called amyloids in various organs leads to amyloidosis. In the heart, this can lead to restrictive cardiomyopathy, congestive heart failure, and sudden death. The common protein precursors for amyloidosis are amyloid immunoglobulin light-chain(AL) and amyloid transthyretin(ATTR). Diagnosis is often delayed, and endomyocardial biopsy, though the gold standard, carries risks. The hereditary subtype(ATTRv-CM) is rare, while the wild-type allele of the TTR gene subtype(ATTRwt-CM) is increasing due to aging population. 99m Tc-pyrophosphate (PYP) imaging is a safe, sensitive method to detect amyloid deposition, crucial for early treatment in the era of emerging therapies for ATTR cardiomyopathy. Materials and Methods: The population of interest for this study included 47 patients who underwent a PYP scan for suspected cardiac amyloidosis between November 2022 to September 2023. We reviewed patient clinical history, laboratory studies, imaging results and therapy related information. All PYP scans were performed by injection of 15 mCi Tc-99mPyrophosphate followed by wholebody-images in the supine position were captured at 1 and 3 hours. Qualitative grade of myocardial uptake was obtained ranging from 0 to3 (0 – no cardiac uptake, 1 – cardiac uptake less than rib, 2 and 3 – cardiac uptake equal to or greater than rib uptake). Heart to contralateral lung ratios (H:CL) were obtained. Additionally, qualitative visual assessment of SPECT imaging was performed. A scan was considered positive with H:CL ratio of >1.5 and grade of myocardial uptake 2 or 3, with SPECT confirmation of uptake in the myocardium. A scan was considered equivocal with H:CL ratio of 1.3 – 1.5, a grade of 2. A scan was considered negative with H:CL ratio of < 1.5 with a grade of 0 or 1.
Results:
Patient Data
| Positive PYP scan | Equivocal PYP scan | Negative PYP scan | |
|---|---|---|---|
| Number of patients | 6 | 12 | 35 |
| Median age years | 65.5 | 60.9 | 54.5 |
| Gender (male: female) | 4:2 | 8:4 | 19:16 |
| Preserved EF (>45%), n (%) | 6 (100) | 11 (91) | 28 (80) |
| LVH, n (%) | 6 (100) | 10 (83) | 14 (40) |
EF: Ejection fraction, PYP: Pyrophosphate, LVH: Left ventricular hypertrophy
The biomarkers NT pro BNP as well as the interventricular septal end diastolic thickness (IVSed) seen on echocardiogram, were all found to be statistically higher in PYP positive cases. One patient with a positive PYP scan underwent therapy specific for cardiac amyloid.
Predictive Markers
| Mean EF % | Mean IVSed (cm) | Mean NT-proBNP | |
|---|---|---|---|
| Positive PYP | 59 | 1.4 | 870 |
| Equivocal PYP | 53 | 1.1 | 772 |
| Negative PYP | 47 | 0.9 | 450 |
EF: Ejection fraction, PYP: Pyrophosphate, IVSed: Interventricular septal end diastolic thickness, NT proBNP: N-terminal pro–B-type natriuretic peptide
One positive PYP patient underwent cardiac MRI and PET/CT for sarcoid and both were positive for inflammation possibly indicating coexistence of both the conditions. Conclusion: The PYP scan has emerged as a non invasive, low cost, low risk imaging study that helps in the diagnosis of ATTR amyloidosis. High sensitivity and specificity of the test have resulted in limited need for endomyocardial biopsy, reinforcing significance of this imaging modality prior to starting appropriate therapy.
Cardio 4: 18 FDG PETCT as a utility in the assessment of secondary infective/inflammatory changes in suspected infective endocarditis or cardiac device related infection
Althaf K M, Rajesh Kumar, Sameer Taywade, Deepanksha Datta
Department of Nuclear Medicine, AIIMS, Jodhpur, Rajasthan, India
Introduction: 18 FDG PET/CT has been recognized as an important tool in the diagnosis of infective endocarditis (IE). It has been included as a major imaging criteria in 2023 Duke's and ESC (European society of Cardiology) criteria for infective endocarditis. This study attempts to assess the role of 18 FDG PET/CT in detecting the secondary changes of inflammation/infection in suspected cases of IE or cardiac device related infection. Materials and Methods: Retrospectively included 16 suspected IE or cardiac device related infection patients who underwent a 18 FDG PET/CT (60 min of FDG injection in myocardial suppression protocol) in our department from January 2021 to September 2023. Those values with SUV more than liver SUV is considered as positive. Two groups were made based on cardiac uptake(+/-). Chi square test was used to compare the characteristics of both groups. P-value <0.05 is considered as significant. Results: Median age was 48 years, Eleven out of sixteen were male patients. Cases include 7 suspected native valve endocarditis (NVE), 4 prosthetic valve endocarditis (PVE) and 5 stent infection. Eight cases were showed a positive cardiac uptake and 8 were not, their median SUVmax were 4.65 and 2.9, respectively. Secondary infective/inflammatory changes were detected in definite cases of IE include; pleural effusion (2/8), Reactive lymphadenopathy (5/8), Pleural effusion (2/8), Diffuse splenic hypermetabolism (6/8), splenic septic infarct (2/8), diffuse hypermetabolic bone marrow (3/8), septic infarct in brain (1/8). Rejected IE group showed; reactive lymph node enlargement 1/8, splenic hypermetabolism 2/8 and bone marrow hypermetabolism in 5/8 patients. Significantly increased splenic hypermetabolism(p-0.04) and reactive lymphadenopathy (p-0.03) are noted in cardiac uptake (+) group. Conclusion: 18 FDG PET/CT can be used as a useful tool to assess secondary infective/inflammatory changes in IE patients and thus increases the confidence in reporting true positive IE and guides in further patient management.
Cardio 5: Unveiling coronary microvascular dysfunction with 13N-NH3 PET – Myocardial flow reserve: The emerging frontier for symptomatic non-obstructive coronary artery disease patients
Vinisha Gunasekaran, V. Gunasekaran, H. Singh, A. Sood, P. Panda, B. R. Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: Nearly half of the symptomatic patients undergoing invasive coronary angiography do not have obstructive coronary artery disease (CAD). Such patients usually have functional disorder of the epicardial vessels or microvasculature or both. 2/3rd of non-obstructive CAD (NOCAD) patients has coronary microvascular dysfunction (CMD) and are at an increased risk of developing major adverse cardiac events. Although invasive methods represent the gold standard for diagnosing CMD, the diagnostic challenges posed by CMD necessitate the development of non-invasive imaging techniques that can reliably detect microvascular dysfunction. One such non-invasive technique is cardiac positron emission tomography (PET) by quantifying reductions in hyperemic myocardial blood flow (MBF) and/or myocardial flow reserve (MFR). This prospective observational study, aimed to quantify MBF and MFR using 13N-NH3 stress/ rest cardiac PET, in patients with suspected CMD. Materials and Methods: 30 symptomatic (angina or angina equivalents), therapy naive patients with NOCAD in invasive coronary angiography, were prospectively enrolled in this study between January 2021 and January 2023. Absolute quantification of MBF in ml/min/gm and MFR were obtained, using a dynamic rest and stress protocol with intravenous adenosine (140 mcg/kg/min, 6-minute protocol) as a hyperemic agent and 400 MBq of 13N-NH3 as PET perfusion tracer. Patients with MFR values <2.3 were considered to have microvascular dysfunction. Results: In the 30 patients (16 males; mean age: 52.5 ± 9.9 years) recruited, 90 vascular territories were assessed. The mean global stress MBF and MFR were 2.54 ± 0.72 ml/min/gm and 2.91 ± 0.81 respectively. 8 patients (CMD group; 27%) had reduced global MFR <2.3 (mean 1.80 ± 0.36) and the remaining 22 patients (reference group; 73%) had normal MFR values. In the CMD group, 3 patients had functional CMD with high resting MBF than the reference group {more than almost twice of the median global resting MBF of reference group (1.72 vs 0.79)} and rest of the 5 patients had structural CMD with blunted response to vasodilator stress test. Relative perfusion abnormality was seen in 16 of 30 patients but only 7 (44%) of them had reduced regional or global MFR. The remaining 9 patients with perfusion abnormality on PET perfusion imaging had normal MFR and adequate contractility. There was no statistically significant association between the presence of perfusion defects and reduced MFR (p = 0.564) or stress MBF (p = 0.648).
Conclusion:
PET is an excellent non-invasive modality for diagnosing CMD in NOCAD patients due to its ability to quantify reductions in hyperemic MBF and MFR.
It can also help in categorizing CMD patients into structural and functional group which aids in understanding the pathophysiology better and formulating personalised treatment regimens.
With normal coronaries, the presence or absence of perfusion defects alone does not rule in or rule out CMD and these defects should be interpreted in light of dynamic PET parameters such as MFR.
Cardio 6: Comparative analysis of occupational effective dose and imaging time in MPI: D-SPECT versus conventional SPECT/CT
Ajay Kumar, A. Kumar, K. Kaur, H. Singh, B. R. Mittal
Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Introduction: Dedicated cardiac SPECT cameras such as the D-SPECT (Spectrum Dynamics) have been designed specifically for myocardial perfusion imaging studies. Equipped with cadmium-zinc-telluride (CZT)–based detectors, the D-SPECT has been exhibited to have image quality superior to that of standard SPECT/CT while reducing patient and personnel radiation exposure and decreasing imaging time. This study aims to compare the whole-body effective dose received by occupational worker and imaging time during MPI acquisition on D-SPECT and conventional Philips SPECT/CT camera. Materials and Methods: 263 patients underwent myocardial perfusion imaging using two systems: DSPECT and Philips SPECT/CT (only stress imaging was included). D-SPECT had two groups: Group I (N = 117) received standard 9-11 mCi of 99mTc MIBI, while Group II (N = 48) received reduced dose of 5-6mCi. Philips camera group (N = 98) received standard 9-11mCi of 99mTc-MIBI. DSPECT acquired images (for 1 million LV counts) in both upright and supine positions to help compensate for subdiaphragmatic artifacts, with noted acquisition times. The whole-body effective dose to occupational workers during patient positioning was measured using electronic pocket dosimeters. Statistical analysis included the Kolmogorov-Smirnov test for data normality and the Mann-Whitney U test to compare effective dose and imaging time between groups: Philips 10mCi vs. D-SPECT 10mCi, Philips 10mCi vs. D-SPECT 6mCi and D-SPECT 10mCi vs. D-SPECT 6mCi. Results: For all the three groups, Kolmogorov-Smirnov test showed p value = 0.0001. Therefore, data was not normally distributed. Philips 10mCi vs. DSPECT 10mCi Group: Philips 10mCi group with mean injected activity 10.202 ± 0.649 mCi received an average dose of 0.163 ± 0.371 µSv per patient, while DSPECT 10mCi group with mean injected activity 10.437 ± 0.731 mCi received a significantly higher dose of 0.769 ± 0.498 µSv per patient (p value = 0.0001). Philips 10mCi vs. DSPECT 6mCi Group: Effective dose was similar between the Philips 10mCi group (0.163 ± 0.371 µSv per patient) and the DSPECT 6mCi group (0.224 ± 0.441 µSv per patient) with a non-significant difference (p value = 0.368). DSPECT 10mCi vs. DSPECT 6mCi Group: DSPECT 10mCi group received effective dose of 0.769 ± 0.498 µSv per patient, significantly higher than the DSPECT 6mCi group's effective dose of 0.224 ± 0.441 µSv per patient (p value = 0.0001). Further considerable differences in the acquisition time were noted. Average Imaging time taken by the Philips 10mCi group, DSPECT 10mCi group and DSPECT 6mCi group were 14.30 min, 8.706 ± .977 min, and 14.832 ± 2.062 min respectively. Conclusion: D-SPECT 10mCi group provided reduced imaging time and better patient throughput at expense of 3-5 folds higher effective dose per patient to occupational worker. D-SPECT 6mCi group provides equivalent image quality and lesser effective dose to technologist, but acquisition time was similar to conventional gamma camera.
Cardio 7: Additive value of cardiac dyssynchrony parameters using rest myocardial perfusion spect in the diagnosis of cardiac sarcoidosis – A cross-sectional analytical study
Kabilash D, Dhanapathi Halanaik, Harinee Ganesan, Harish Goyal
Department of Nuclear Medicine, JIPMER, Pondicherry, India
Introduction: Sarcoidosis is a complex, multisystemic inflammatory disorder. Cardiac involvement in sarcoidosis is associated with poor prognosis. Early diagnosis of cardiac sarcoidosis is crucial for early treatment to avoid significant mortality and morbidity associated with post-inflammatory sequelae. Current guidelines recommend a combination of myocardial perfusion imaging by sestamibi single photon Emission Computed Tomography (MPI SPECT) and inflammation imaging either by F-18 FDG or Ga68 -DOTA-NOC for detecting the focus of inflammation in patients with clinically suspected cardiac sarcoidosis. Cardiac dyssynchrony parameters using MPI SPECT have been studied in patients undergoing resynchronisation therapy. However, the role of these parameters is not explored in patients with cardiac sarcoidosis. Hence this retrospective study is undertaken to assess the utility of cardiac dyssynchrony parameters using MPI SPECT in patients suspected with cardiac sarcoidosis. Materials and Methods: This retrospective, descriptive study was conducted at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry. We reviewed 27 patients’ data from suspected sarcoidosis patients who underwent imaging from February 2020 to March 2022. The 99mTc SESTAMIBI-SPECT images were reviewed, and the phase dyssynchrony parameters of all these patients were calculated using the Emory cardiac toolbox. The mean and standard of the dyssynchrony parameters (phase standard deviation, phase histogram bandwidth) were compared among those who had inflammation in 18F-FDG and/or 68Ga-DOTANOC imaging and those without. The student's t-test was used to compare the dyssynchrony parameters among the two groups. A p-value < 0.05 was considered to be statistically significant. The dyssynchrony parameters of positive patients were also compared with the normal healthy indian population already published in the literature. Results: 9 out of 22 patients were positive for active cardiac inflammation. The phase standard deviation was found to be higher in the negative group (51.13 ± 29.21) than the positive group (43.05 ± 24.03), but not statistically significant (p-value 0.22). The phase histogram bandwidth was also found to be higher in the negative group (143.23 ± 78.13) than the positive group (108.11 ± 62.31), but not statistically significant. However, the phase dyssynchrony parameters were statistically significantly higher in the positive group when compared to the normal healthy population. The Phase SD in females in positive group (42.62 ± 22.49) was significantly higher than the normal healthy female population (7.7 ± 2.7) (p-value 0.02). The Phase BW in females in positive group (115.2 ± 64.91) was significantly higher than the normal healthy female population (25.3 ± 8.6) (p-value 0.03). But, the phase dyssynchrony parameters in the male population could not be compared with the normal population since the sample size was too low for comparison. Conclusion: Cardiac dyssynchrony parameters could not be used for diagnosis in cardiac sarcoidosis patients. But it may have a role in assessing the response to treatment. Our study did not probe into response evaluation. Further studies are warranted. The utility of these parameters in early diagnosis should be evaluated in further studies.
Cardio 8: Effect of change of reconstruction parameters on NH3 PET/CT cardiac images in patients undergoing myocardial flow reserve study
Vishal Nimesh, V. Nimesh, N. Rana, M. Parmar, R. Kumar, B. R. Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: Cardiovascular disease (CVD) is a leading cause of death worldwide. The quantification of MFR with pharmacologic vasodilation can help in the identification of coronary functional abnormalities at an early stage before the clinical manifestation of coronary artery disease. Positron emission tomography/computed tomography (PET/CT) with nitrogen-13-labeled ammonia (NH3) is an essential tool for assessing myocardial perfusion and flow reserve. Image quality and quantification are influenced by various factors, including the reconstruction parameters. The aim of the study was to investigate the impact of changing reconstruction parameters on NH3 PET/CT cardiac image quality and quantification in patients who underwent MFR assessment. Materials and Methods: A total of 9 patients (5 males and 4 females with mean age 61.6 years) underwent 13N-ammonia PET/CT cardiac perfusion studies using a hybrid PET/CT scanner (Discovery 710, GE Healthcare, Milwaukee, USA). A low-dose CT (140 kV, 20 mA) with the heart in the field of view, followed by two dynamic PET acquisitions after on-table administration of 13N-ammonia was done. The PET acquisitions were done in LIST mode in two phases of 12 minutes each: the rest phase, followed by the stress phase after the induction of pharmaceutical stress. Adenosine was used as a cardiac pharmacological stress agent with an administration rate of 140µg/kg/min infusion for 6 minutes. Images were reconstructed using the iterative reconstruction (IR) and the filter-back projection (FBP) method. The reconstruction parameters for IR were 128×128 matrix size, 32 subsets, 2 iterations and standard filter with 6.4mm cutoff. Fourier filtered back projection method employed matrix size of 128×128, Hanning filter with order 5 and cut off of 12mm. In both set of reconstructed images MFR (MFRIR, MFRFBP) and four more quantitative parameters, Ejection fraction (EFIR,EFFBP), End systolic volume(ESVIR,ESVFBP), End diastolic volume(EDVIR,EDVFBP), Systolic volume(SVIR,SVFBP) were calculated each for rest and stress study. The mean values of all the 9 parameters using both reconstruction methods were compared using paired t test. The difference was considered statistically significant for p <0.05. Results: The mean value of MFRIR and MFRFBP were 2.19 and 2.32. For stress study the mean values of EF, EDV, ESV and SV (IR vs. FBP) were. 66.0% vs. 66.0%, 92.67ml vs. 93ml, 31.33ml vs. 31.89ml, and 61.33ml vs. 61.11ml. For the rest study, the values were 66.0% vs. 66.0%, 87.28ml vs. 87.89ml, 31.33ml vs. 30.78ml, and 56.44ml vs. 57.11ml. Respectively There was no statistically significant difference in the mean value of all 9 quantitative parameters in the images reconstructed using IR and FBP method. Conclusion: There was no significant difference in the MFR and other quantitative parameters using different reconstruction methods. However the effect of change of reconstruction methods on image quality needs to be validated with a larger number of patients and also with correlation with visual image quality of the images.
Cardio 9: To evaluate the correlation between Biochemical blood parameters and disease status on [18F]FDG PET/CT scan in patients with Takayasu Arteritis
Richa Maurya, Vijay Singh, Manish Ora, Sanjay Gambhir
Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: Takayasu Arteritis (TA) is a rare inflammatory disorder affecting large arteries, such as the aorta and branches. TA can impair patients’ quality of life and present a diagnostic challenge for clinicians because of its diverse clinical manifestations. The diagnosis and assessment of disease activity in TA are challenging due to the lack of specific clinical and laboratory markers. The diagnosis requires clinical evaluation, laboratory parameters, and imaging studies. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complete blood count provide indirect evidence and support the clinical diagnosis. FDG PET/CT is a non-invasive imaging modalityincreasingly used to elucidate inflammation. It detects the presence and extent of active arterial inflammation and helps to differentiate the persistent chronic anatomical changes. We evaluate the correlation of inflammatory markers with FDG PET/CT findings. Materials and Methods: This study involved a retrospective analysis of a cohort of 50 patients. We collected comprehensive baseline demographic information, such as age, gender, and relevant medical history. The routine laboratory investigations measured ESR and CRP. [18F]FDG PET/CT scans were done as per the standard protocols. SUV max of the involved vessels was gathered from the FDG PET/CT findings. SPSS software was used for the statistical analysis, and the Spearman correlation coefficient was calculated with the SUV max of the involved vessel with ESR and CRP. We took anSUV cut-off of 2.0 to differentiate between disease activity. Results: Out of 50 patients, 38 (78%) were female. Active disease was noted in 19 patients (39%), and disease in the remission period was noted in 30 patients (61%). The mean ESR and CRP were 40.1 mm/hr (5.0-140, SD = 28) and 3.3 iu/ml (0-68.2, SD = 10.0). The mean SUV max was 3.4 (0-8.9, SD = 1.5). Out of 49 patients,19 patients (39 %) had ESR < 30 mm/hr, and the rest 30 patients (61 %/) had ESR > 30mm/hr. In patients with ESR<30 mm/hr group, three patients (16%) had active disease, while in patients with ESR >30 mm/hr group, 17 patients (57%) had active disease. Out of the total patients, 28 patients (57%) had a normal CRP (< 1 IU), while the rest 21 patients (43%) had raised CRP. Only three patients (11%) had active disease in the group with normal CRP value, while the rest were disease-free. In patients with the raised CRP group, 17 patients (81%) had active disease, while the rest were disease-free. Amild positive correlation (r = 0.28, p-value =0.22) was noted between ESR and SUV max of the involved vessel, and a mild positive correlation (r = 0.27, P value = 0.24) was also noted between CRP and SUV max of the involved vessel [Table 1].

Conclusion: There is a weak correlation between inflammatory markers and functional imaging. Based on [18F]FDG PET/CT findings, 16 % of the patients with normal ESR and 11% with normal CRP had active vasculitis. This could be due to less area of disease not amounting to raise the systemic inflammatory markers. In patients with raised inflammatory markers,43 % with raised ESR and 19% with raised CRP had no active disease. This emphasizesthem being non-specific markers for vasculitis. PET/CT may disclose nonvascular areas of active inflammation in these patients.
| Parameters | Correlation | SUVmax |
|---|---|---|
| ESR | Spearman correlation | 0.28 |
| Significant (two-tailed) | 0.22 | |
| CRP | Spearman correlation | 0.27 |
| Significant (two-tailed) | 0.24 |
Correlation is significant at the 0.01 level (two-tailed). ESR: Erythrocyte sedimentation rate, CRP: C-reactive protein, SUVmax: Maximum standardized uptake value
Category: Endocrinology
Endo 1: Precision in practice: Our center's expertise in parathyroid scintigraphy for detecting and localizing parathyroid adenomas/hyperplasia
Priyamedha Bose Thakur, Satyawati Deswal, Lavish Kakkar, Mohammed Khalid
Departments of Nuclear Medicine, Dr. Ram Manohar Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: This study aims to evaluate the precision and clinical applicability of parathyroid scintigraphy in detecting and precisely localizing parathyroid adenomas/hyperplasia and Brown tumors across different forms of hyperparathyroidism. Materials and Methods: Conducted at a tertiary care hospital in India, this retrospective investigation involved patients referred to the Nuclear Medicine department from January 2022 to June 2023. Patient histories were recorded, followed by comprehensive physical examinations. Measurements of Intact Parathyroid Hormone (iPTH), total serum calcium, serum Vitamin D3, and serum creatinine levels were collected before imaging. Adhering to SNMMI Practice Guidelines for Parathyroid Scintigraphy 4.0, parathyroid scintigraphy was carried out, utilizing a Dual Phase Tc99m-sestamibi protocol with SPECT/CT for imaging. Certain patients underwent whole-body planar imaging with regional SPECT/CT to enhance adenoma localization and visualize Brown tumors. Results: Among the 30 patients referred within an 18-month period, 23 were suspected primary, 5 secondary, and 2 tertiary hyperparathyroidism cases. Out of 23 primary hyperparathyroidism patients, 21 were positive, with 4 exhibiting multiple Brown tumors showing increased Tc99m sestamibi avidity on whole-body planar imaging. Notably, a case with extremely elevated serum PTH (1074 ng/ml) was scintigraphically positive and later histopathologically confirmed as Parathyroid carcinoma. All secondary hyperparathyroidism cases, linked to Chronic Kidney disease and elevated serum creatinine, were negative on scintigraphy. Suspected tertiary hyperparathyroidism cases also showed negative imaging. Among 11 scintigraphy-positive patients, 7 underwent focused parathyroidectomy with a minimal 2.5 cm incision, while the remaining 4 had hemithyroidectomy/total thyroidectomy combined with parathyroidectomy with a conventional Kocher's incision due to incidentally identified high-risk (TIRADS 4 or 5) thyroid nodules during the preoperative ultrasounds. Intraoperative findings and postoperative histopathology confirmed accurate detection and localization of scintigraphy-positive parathyroid adenomas. Conclusions: Our center's experience underscores the high sensitivity of Parathyroid Scintigraphy in identifying solitary parathyroid adenomas in Primary Hyperparathyroidism. Augmenting the protocol with whole-body planar and regional SPECT/CT imaging effectively detects Brown tumors linked to prolonged untreated hyperparathyroidism. However, scintigraphy's efficacy is limited in detecting parathyroid hyperplasia in secondary hyperparathyroidism. Despite its utility, preoperative scintigraphy for ectopic parathyroid glands in secondary hyperthyroidism cases possesses low sensitivity and doesn't replace the necessity of bilateral neck exploration. This study illuminates the nuanced applications of Parathyroid Scintigraphy, contributing valuable insights to its clinical use.
Endo 2: 18F FDG PET/CT imaging pattern of the most prevalent adrenal lesions
Man Mohan Singh, L. Kakkar, P. Bose Thakur, S. Deswal
Department of Nuclear Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: 18F FDG PET/CT is the useful imaging tool for various adrenal lesions. It may be difficult to differentiate various adrenal lesions without careful correlation with the patients’ histories, laboratory test and other imaging findings. The purpose of our study was to evaluate the characteristic spectrum and FDG uptake pattern of adrenal lesions in 18F FDG PET/CT. Materials and Methods: We retrospectively assessed routinely performed oncological 18F FDG PET/CT scan data of patients having histologically proven primary or adrenal lesion / diagnosed on other anatomical imaging modality. Results: We present a pictorial case series highlighting the characteristic FDG uptake pattern in a spectrum of various adrenal lesions including normal, hyperplasia/ hypertrophy, adenoma, carcinoma, metastasis (unilateral and bilateral), pheocromocytoma, myelolipoma and lymphoma on 18F FDG PET/CT scan. Conclusion: FDG PET/CT is powerful tool to evaluate the adrenal lesions. Knowledge of characteristic spectrum and pattern of FDG uptake of adrenal lesions is helpful for increasing diagnostic accuracy in reading of FDG PET/CT scan and expending the differential diagnosis.
Endo 3: Ga-68 pentixafor PET/CT as a novel diagnostic non-invasive tool for determining the subtype of primary aldosteronism: A case series
K. Ashish Acharya, M. Indirani, Shelley Simon
Department of Nuclear Medicine, Apollo Hospitals, Chennai, Tamil Nadu, India
Introduction: One of the most common causes of secondary hypertension is primary aldosteronism (PA). Aldosterone producing adenoma (APA) and bilateral adrenal hyperplasia (BAH) are the common causes of primary hyperaldosteronism. It is important to distinguish between APA and BAH in patients with proven PA since surgical intervention is advised for APA and medical management in the form of oral mineralocorticoid receptor antagonists for BAH. The current methods for subtyping PA are adrenal vein sampling (AVS) and CT. AVS is invasive and technically challenging, whereas CT has an accuracy of only 50-70%. Adrenal CXC chemokine receptor type 4 (CXCR4) expression is found in zona glomerulosa of adrenal cortex, and is significantly higher in APAs than in normal adrenal tissue as well as non-functional tumors. Pentixafor, a specific ligand for CXCR4 labelled with 68Ga, proves beneficial in PA subtyping. Materials and Methods: This was a prospective study conducted at our institute from January 2023 to September 2023, consisting of 5 patients. The inclusion criteria included patients: i) diagnosed with PA clinically (Resistant hypertension) & biochemically (plasma aldosterone > 16 ng/dl, serum potassium< 3.5mEq/l, aldosterone: renin ratio of >30 ng/dl per ng/ml/hr) ii) unsuitable for AVS. Patients diagnosed with PA underwent Ga-68 Pentixafor PET/CT. Dose of 0.05 mCi/kg was administered intravenously and PET/CT whole body scan was acquired after 1 hour. Adrenal nodule with focal increased tracer uptake was considered to be APA. Diffuse increased tracer uptake was considered to be BAH. In case of APA, the SUVmax was obtained by drawing ROI on the nodule showing focal tracer uptake, whereas in BAH, ROI was drawn on both the adrenals to obtain SUVmax. Results: Out of the 5 patients with biochemically proven PA, 4 were diagnosed with APA and 1 with BAH on Ga-68 Pentixafor PET/CT. SUVmax of APA was significantly higher (21.6, 7.8, 7.5 & 12.6) than BAH (4.9 & 4.3 in left and right adrenals respectively), both of which were higher than average adrenal SUVmax measured in non-PA (control) patients (3.1). The 4 patients with APA underwent adrenalectomy following which histopathological and immunohistochemical diagnosis confirmed the same (100 % accuracy). All 4 patients had complete biochemical remission following surgery. The one case with BAH was started on medical management and biochemical remission was obtained.
| Patient | Diagnosis | SUVmax of adrenal |
|---|---|---|
| 1 | APA | 21.6 (right) |
| 2 | APA | 7.8 (left) |
| 3 | APA | 7.5 (left) |
| 4 | APA | 12.6 (right) |
| 5 | BAH | 4.9 (left), 4.3 (right) |
APA: Aldosterone producing adenoma, BAH: Bilateral adrenal hyperplasia, SUVmax: Maximum standardized uptake value
Conclusion: Ga-68 Pentixafor PET/CT is a promising non-invasive method which can be an alternative or an adjunct for AVS when it is inconclusive/non-diagnostic/contraindicated. It has a proven sensitivity and specificity for detecting primary aldosteronism.
Endo 4: Preoperative localization of parathyroid adenomas: The value of F-18-choline PET/CT in patients with negative findings on 99mTc-sestamibi SPECT/CT
Mrinalini Koley, D. Malik, P. Thakral, S. S. Das, J. Gupta, Jyotsna, N. Singh, N. Rana, I. B. Sen
Department of Nuclear Medicine, FMRI, Gurugram, Haryana, India
Introduction: Primary hyperparathyroidism (PHPT) is a common endocrine abnormality, caused in most cases by a single parathyroid adenoma. Surgery remains the first-line curative therapy in PHPT. Single-photon scintigraphy with 99mTc-Sestamibi with or without SPECT or SPECT/CT is part of the standard of care for preoperative localization of parathyroid adenomas in many centers with availability and expertise in nuclear medicine, however it is less accurate for detecting abnormal parathyroid tissue in patients with small adenomas, multiglandular disease, superior adenomas, or preoperative normocalcemia. Parathyroid radionuclide imaging with F-18 Fluoro Choline PET/CT is a highly sensitive procedure for the assessment of the presence and number of hyperfunctioning parathyroid glands. Here, we aim to assess the Value of F-18-Choline PET/CT in Patients with Negative or Discordant Findings on 99mTc-Sestamibi SPECT/CT. Materials and Methods: Forty-one patients with biologically proven primary hyperparathyroidism (elevated parathyroid hormone [PTH] levels or normal PTH despite hypercalcemia) and negative or discordant results on 99mTc-sestamibi scan were assessed using F-18-choline PET/CT and underwent parathyroid exploration. Patients found to have parathyroid adenoma intraoperatively with post-operative histopathological confirmation were considered as true positives. Chi square tests were applied for assessing sensitivity and specificity. Results: Out of 28 patients with positive F-18 choline PET/CT findings, 27 were found to be true positive. 1 patient with positive lesion in PET CT was postoperatively found to be a lymph node. Only 4 out 13 patients with negative F-18 choline scan were found to have parathyroid adenoma intraoperatively, with postoperative histopathological confirmation. Statistical analysis found chi square value of 20.7 (p value < 0.01), with sensitivity of 87.10%, specificity of 90.00%, PPV 96% and NPV 69.23%. Accuracy of the test was found to be 87.80%. Conclusion: The results indicate that F-18-choline PET/CT has a high sensitivity, specificity and accuracy, and is a promising tool for preoperative parathyroid adenoma localization when 99mTc-sestamibi imaging with or without SPECT/CT yield negative or discordant results.
Endo 5: Brown fat activity in the diagnosis of disease progression in paraganglioma
D. Kabilash, Harinee Ganesan
Department of Nuclear Medicine, JIPMER, Pondicherry, India
Introduction: Paragangliomas are rare, usually benign catecholamine-secreting neuroendocrine tumors. A small percentage of these can transform into malignant tumors. These tumors also show FDG avidity, both benign and malignant. 18F-FDG uptake in regions of brown fat distribution is a common incidental finding and may mimic a tumor uptake. Cold exposure or food intake can stimulate brown fat, and activated brown fat increases glucose uptake. Apart from these factors, brown fat is known to have abundant adrenergic receptors, and their expression has been found to be increased in cases of pheochromocytoma. This report presents a case where FDG brown fat uptake was found when definite disease progression was noted in other regions. Materials and Methods: A 41-year-old female patient presented with swelling and numbness in the left upper limb for 3 months. Radiological evaluation of the neck region revealed an enhancing irregular soft tissue mass lesion in the left first rib with bony destruction of it and the first vertebra. Cytology from the lesion showed metastatic carcinoma. 18F-FDG PET/CT was done as a baseline. Histopathological evaluation of the right level II cervical lymph node showed evidence of paraganglioma. She had no headache, sweating, tremors, palpitations, excessive anger, or hypertension symptoms. 68Ga-DOTANOC imaging was done, and it showed somatostatin receptor expression of all the lesions. She was given three cycles of conventional chemotherapy with CVD regimen. In view of nephrotoxicity, she was referred for PRRT. She was given 3 cycles of 177Lu-DOTATATE therapy. Follow-up blood counts revealed thrombocytopenia. She defaulted after that. 2 years later, she presented again with a low backache. FDG PET/CT was done to evaluate the current disease status. Results: Baseline FDG PET/CT showed metabolically active multiple intervertebral lesions in the thoracic and lumbar vertebrae, left hip bone, multiple liver lesions, solitary right lung lesion, and cervical and abdominal lymph nodal metastases causing right ureter compression and upstream right-sided hydroureteronephrosis. Increased metabolic activity is also noted in bilateral perirenal adipose tissue. 2 years later, follow-up FDG PET/CT revealed an increase in the number and size of intervertebral lesions, an increase in the number and size of hepatic and lymph nodal metastasis, and the onset of a new lesion in the left temporal bone. Apart from these findings, perirenal fat showed diffusely increased FDG uptake, which was also found earlier in the baseline study. Conclusion: Increased brown fat uptake is noted both in the baseline and during disease progression, confirming that it does not depend on the environmental conditions during the image acquisition. Furthermore, the increase in the metabolic activity in the brown fat is found to correlate with the disease progression.
Endo 6: Cystic pheochromocytoma - a scintigraphic diagnosis
Harinee G, Dr. Kabilash D
JIPMER
Introduction: Cystic adrenal masses are a relatively rare condition and are usually non-functioning and asymptomatic. Only a few cases of cystic pheochromocytomas have been reported in the world literature. Here, we report a 35-year-old female presenting with abdominal pain and classical symptoms of pheochromocytoma, showing 131I-mIBG avid suprarenal cystic lesion, confirming Pheochromocytoma. Materials and methods: The patient presented with a history of pain in the abdomen for one month, radiating to the back, and associated with chest discomfort and vomiting. History of intermittent headache, sweating, and palpitations present. History of reduced urine output, shortness of breath, and significant loss of weight. There is no history of fever, abdominal distention, hematemesis, or constipation. Blood pressure was occasionally high. Ultrasound showed a solid lesion with necrotic changes in the left para-aortic region anterior to the left renal vessels. Echocardiography showed apical LV, mid septum, and mid anterior septum hypokinesia and moderate LV dysfunction. Contrast-enhanced CT revealed a cystic lesion with an irregular, thick, enhancing wall in the left suprarenal region. The left adrenal gland could not be separately visualized. Urinary VMA was elevated at 10.6 mg/24hrs. 131I-mIBG scintigraphy was then performed in order to confirm the diagnosis and to define the site of primary and metastatic involvement of other sites. Results: Whole body I-131 mIBG revealed mild increased tracer uptake in the left suprarenal region. The corresponding CT scan showed a large peripherally enhancing cystic lesion in the corresponding area. Conclusion: This case underscores the importance of 131I-mIBG scintigraphy in the diagnosis of cystic pheochromocytoma.
Endo 7: Assessment of dynamic parameters of 99mTcO4- pertechnetate during thyroid scintigraphy in hyperthyroidism
K. Vidhya, Meena Negi, Vandana K. Dhingra
Department of Nuclear Medicine, AIIMS, Rishikesh, Uttarakhand, India
Introduction: Thyroid scintigraphy in it's standard mode involves static imaging at 20 minutes. Absolute pertechnetate uptake and thyroid to parotid ratio is usually used in addition to images to diagnose thyroid function disorders. Thyroid disorders like thyrotoxicosis, thyroiditis and thyroid nodules involve altered functional dynamics of blood flow, pertechnetate uptake uptake and iodine metabolism within the gland. These can have potential to be utilized in diagnosis using dynamic imaging. Methods: A total of 19 Patients diagnosed with Hyperthyroidism were included in this prospective study for Dynamic 99mTcO4- Pertechnetate thyroid scintigraphy. In this study, 4-5mCi of 99mTcO4- was injected intravenously to the patient under a gamma camera. Immediate flow images, early blood pool for 3min & dynamic imaging was performed for 19min. Static Images of thyroid gland were taken immediately after the 1st and 20thMinute of the study. In addition, thyroid spot images (Obliques and Marker) were taken. Regional SPECT/CT of neck was also done (if needed). For all patients, the uptake with the mean and standard deviation were calculated at 1min and 20min imaging and correlated clinically. Results: A total of 19 patients diagnosed with Hyperthyroidism were enrolled in the study. For all patients, the uptake with (mean value ± SD) of thyroid anterior image at 1min and 20min were (132006.2 ± 101797.8) & (233800.6 ± 171189.0) respectively. The maximum: minimum counts at 1min and 20min were 329468: 19960 & 537556: 34023 respectively. Conclusion: In this pilot study we assessed dynamic imaging parameters during pertechnetate imaging. Our study findings demonstrate that in cases of hyperthyroidism, dynamic scintigraphic thyroid gland images taken immediately during the first minute of intravenous injection of 99mTcO4- pertechnetate have potential to provide additional parameters for diagnosis of thyroid function and uptake. Limitations: This method needs further assessment in more numbers of patients and is a potential way to differentiate Graves’ disease from euthyroid glands & thyroiditis.
Endo 8: Estimation of suppressive dose of levothyroxine in thyroid cancer patients – A pilot study in the Indian population
P. Chauhan, V. Singh, M. Ora
Department of Nuclear Medicine, SGPGI, Lucknow, Uttar Pradesh, India
Introduction: ATA category intermediate and high-risk thyroid cancer patients’ post-surgery and remnant ablation need long-term TSH suppression to prevent disease spread and recurrence. The requirement of Levothyroxine dose for such is 2.2-2.7 ug/kg body weight, as suggested by the guidelines. This dose calculation is done mainly by keeping the western population. We hypothesized that Indian body composition contains less lean body mass than the western population. This Levothyroxine dose requirement could be a surplus in the Indian population. This could lead to side-effect related to iatrogenic hyperthyroidism. This study is done to estimate the Levothyroxine dose required to keep the patient in suppression in an Indian scenario. Materials and Methods: We prospectively evaluated data from treated cases of thyroid cancer patients who came for follow-up on an outpatient basis. Demographic status, age, sex, and weight were collected, and the initial ATA risk category was noted. Serum TSH status and the prescribed dosage of Levothyroxine were also noted. Suppressed TSH values were segregated from the data, and the dose per kg was calculated. Mean, median, range, and lowest dose/kg body weight were calculated from the data. Results: A total of 36 patients were included in the study. The total follow-up on suppressed TSH with corresponding Levothyroxine dosage were 90. The median age of the sample size was 39 years (SD- 11.7 yrs, range 20 – 70 yrs). The male-to-female ratio was 1:2. Mean suppressed TSH value was 0.06 (SD- 0.09, range 0.001-0.430 mIU/L). The dose/kg was calculated for each patient, the minimum dose required to keep the patient in suppression was 1.29 ug/kg, and the maximum dose was 3.33 ug/kg. The mean suppressive dose was 2.21 (SD- 0.49, 1.29 – 3.33) ug/kg body weight. 16 (50%) patients had suppressed TSH values with less than 2ug/kg dose. 14 (44%) patients receiving a dosage of more than 2ug/kg were in excess TSH suppression (TSH- 0.01-0.09 mIU/L) as per their risk stratification. Conclusion: In our pilot study, we found a wide variation in the doses of Levothyroixin to keep TSH suppressed. Nearly half of the patients can be in TSH suppression with a dose less than 2ug/kg. Inadvertent prescription of larger Levothyroxin doses as per guidelines leads to excessive suppression of the TSH over and above, as suggested by the risk category. Our pilot study suggests that Serum TSH in Indian thyroid cancer patients can be suppressed with a lower dose of Levothyroxine. It could reduce risks associated with long-term suppression, such as cardiovascular, cognitive, and osteopenia.
Endo 9: Correlation between baseline thyroglobulin, anti-thyroglobulin with American Thyroid Association's risk stratification in differentiated thyroid cancer prior radio-iodine therapy
Meet Patel, Subham Dadhich, Gurudas Singh, Chaitany Kalani, P. Laxmi Thulsi, Karan Peepre
Department of Nuclear Medicine, Mahatma Gandhi Medical Collage and Hospital, Jaipur, Rajasthan, India
Introduction: The prognostic values of serum thyroglobulin (Tg) and anti-thyroglobulin antibody (TgAb) levels, measured immediately before I-131remnant ablation in patients with differentiated thyroid cancer (DTC), Correlation between Tg, TgAb with American Thyroid Association's (ATA) risk stratification in DTC patients, to check the clinical significance of basal serum Tg and TgAb levels and ATA risk stratification in DTC patients. Materials and Methods: In this retrospective study, the records of 32 patients with differentiated thyroid cancer, who had undergone treatment in 2022-2023, were assessed. Of those, patients with results of basal serum thyroglobulin and anti-thyroglobulin were done. Age, sex, tumor histology, basal thyroglobulin (Tg), anti-thyroglobulin (TgAb) and TSH concentration, radioactive iodine doses in each hospitalization, numbers of hospitalization, and risk categorized on basis of ATA were patients are categorized in low, intermediate and high risk. The relationship among basal Tg, TgAb, and ATA basis risk classify and total radioactive iodine doses were assessed. Results: In this retrospective study, the records of 32 patients with differentiated thyroid cancer, on basis of ATA risk stratification 6 in Low risk, 19 in intermediate risk & 7 in high risk correction with Tg and TgAb. Low risk studies correlate with Tg (mean-4.56) and TgAb (mean-3.17) levels (which are lower side in below Tg-10 ng/ml and TgAb-10 IU/ml). In intermediate risk studies also correlate with Tg (mean-14.87) and TgAb (mean-17.21) (which are below Tg-50ng/ml and TgAb-50 IU/ml). High risk studies are not correlate, significant variances in Tg and TgAb. Conclusion: Serum thyroglobulin (Tg) and anti-thyroglobulin antibody (TgAb) levels, in patients with differentiated thyroid cancer (DTC), some positive correlation in Tg, TgAb with low and intermediate risk patients on the basis of ATA risk stratification. High risk patients are not correlated with Tg ad TgAb levels.
Endo 10: [11C]Choline PET/CT in suspected hyperparathyroidism: A case series of biochemical and imaging findings
Vijay Singh, Mohd. Faheem, Manish Ora, Manish Dixit, Sanjay Gambhir
Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: Minimal invasive parathyroidectomy(MiP) has become the standard of care in hyperparathyroidism. Conventional imaging USG and 99m-Tc MIBI parathyroid imaging have a pivotal role. Conventional imaging sometimes falls short in localization, particularly in cases with ectopic parathyroid adenoma, hyperplasia, small glands, and multiglandular disease, making management difficult. 11C-Choline PET/CT, exploiting the high choline kinase expression in parathyroid adenomas, can potentially enhance detection and localization, especiallyin cases that show positive and concordant findings on conventional imaging. Materials and Methods: Four cases with hyperparathyroidism were recruited, and demographic details, clinical history, and biochemical parameters were recorded. All four patients have already undergone primary imaging with USG and 99m-Tc MIBI parathyroid imaging. PET/CT was done with 10 mCi of 11-C-Choline. PET/CT was acquired from the skull base to the heart level after 20 min. Results: All patients were of female gender;the mean age was59.5 years (SD= 9.3), and the Mean calcium and mean PTH were9.5 mg/dl (SD = 1.5)and 80pmol/L (SD = 72.7), respectively. Mean values of Serum phosphorus, serum albumin, VitaminD, and Alkaline phosphate were 3.5 mg/dl (SD = 2.7), 4.1 mg/dl (SD = 0.25), 87.2 nmol/l (SD = 27.2) and 145 gm/dl (SD = 71). MiP was done with the measurement of intraoperative PTH levels (ioPTH). Case 1: The patient presented with backache and normocalcemichyperparathyroidism(S. cal- 9.1, PTH- 32.18 pmol/l). USG was normal. 99m Tc-MIBI scan was suspicious for adenoma. 4DCT was negative for parathyroid adenoma. 11-C Flurocholinewas done, which suggested the right inferior parathyroid adenoma. MiP was done, and ioPTH showed a curative fall in PTH. Histopathological confirmed the parathyroid adenoma. Case 2: The patient presented with a history of multiple fractures and end-stage renal disease. Biochemical parameters are suggestive of hypocalcemic hyperparathyroidism(S. cal- 7.5, PTH- 70.66 pmol/l). On USG, bilateral parathyroid adenoma was suspected;however, a 99m Tc MIBI Scan showed a single right parathyroid adenoma. 11-C Flurochloine was suggestive of multiglandular disease. Right superior, inferior, and left inferior parathyroid lesions were identified. Case 3: The patient presented with asymptomatic hypercalcemia; on further biochemical evaluation, PTH was raised(S. cal- 10.9, PTH- 9.5 pmol/l), However, USG and 99mTC MIBI did not reveal adenoma. PTH level was persistently raised. 11-C Choline PET/CT did not reveal any adenoma. The patient is currently on biochemical follow-up. Case 4: The patient was operated on for 99m Tc-MIBI confirmed parathyroid adenoma two years back. Post-surgery PTH and calcium levels were normal. The patient presented with a rising PTH (S. cal- 9.7, PTH- 91 pmol/l), with normocalcemia. USG scan of the neck was negative forrecurrent parathyroid adenoma. 99m TC MIBI and 4D CT were negative. 11-C choline PET/CT also failed to reveala parathyroid lesion. The patient is currently on follow-up. Conclusion: These scenariosunderscore the clinical utility and value of 11C-Choline PET/CT in challenging hyperparathyroidism. Accurate identification may guide MiP and confirmation of curative ioPTH fall, thus avoiding bilateral neck exploration. Routine C11 choline PET/CT may not be necessary. The modality could be valuable in patients with failed or discordant traditional imaging. It may also aid in the management of the re-operative or multiglandular setting. The outcome of patients with negative 11C Chole PET is largely unknown and is a potential research area.
Category: Hepatology
Hepato 1: Preparation and preclinical evaluation of 99mTc-glibenclamide formulation for detection of pancreatic problems
Sajid Husain, Ashok Chandak, Sajid Husain, Sutapa Rakshit, Yogita Shete, M. K. Ray, Sandip Basu
Radiation Medicine Centre, BARC, Mumbai, Maharashtra, India
Introduction: Diabetes mellitus is result of an absolute or relative reduction in pancreatic beta cell mass leading to insufficient secretion and hypoglycemia. Treatments for diabetes mellitus range from drugs that increase insulin secretion and sensitivity, to insulin administration, to pancreatic islet cell transplantation. Glibenclamide (GBD) is one of the most potent sulfonylurea derivatives used in the treatment of maturity-onset diabetes by inducing insulin secretion in pancreatic β cells. Pancreatic islet cell mass (PICM) is a major element of the insulin secretory capacity in humans which is examined by invasive study. The pancreas is deep in the middle of the body so it is difficult to image with CT and also critical for biopsy. Noninvasive procedures are needed to quantify beta cell mass for monitoring the onset, progression and responses to therapy and to detect rejection in transplant patients. The present work was aimed to assess the pancreatic beta cell in normal healthy rat (animal) using SPECT-CT imaging. Objective: The aim of the present study was to use inhouse optimized stable 99mTc-GBD preparation for imaging of pancreatic glands noninvasively specially the islet cell mass. Materials and Methods: The optimization of the formulation was carried out using different ratio/concentration of the solvents such as PEG 400, ethanol and DMSO and reducing agent SnCl2 .2H2O in the preparation. 10 mCi (± 1.0) 99mTc were added to the drug solution and heat the vial in boiling water bath. Carried out the physicochemical and biological quality control test of the labeled product. Biodistribution studies were carried out of optimized product injected (5 MBq) into the teil vein of the healthy normal Wistar rat and SPECT-CT imaging was done at 45 min 6 hr and 18 hr post injection. Results and Discussion: The product was found clear with pH 5.0 (± 0.2) and obtained reliable overall radiochemical yields and RCP without any chelating agent coupling with GBD. The in-vivo study of normal animal confirms the stability and shows that the drug is deposited very specifically at the pancreas. Conclusion: The 99mTc-GBD is promising RP for imaging the pancreatic islet cell mass and to detect the problems in the initial stage of the disease noninvasively. for imaging of the pancreas is under progress. Standardization of dose in pancreatic tumor animal model evaluation will confirm the utility of the labeled product.
Hepato 2: Formulation optimization, physicochemical evaluation and in-vitro stability of 99mTc labeled with solubilized glibenclamide
Sajid Husain, Ashok Chandak, Sajid Husain, M. K. Ray
Radiation Medicine Centre, BARC, Mumbai, Maharashtra, India
Introduction: Glibenclamide (GBD) is poorly soluble second generation and one of the most potent sulfonylurea derivatives used in the treatment of maturity-onset diabetes as an oral hypoglycaemic agent by inducing insulin secretion in pancreatic β cells. GBD shows solubility in methanol, ethanol, dimethyl sulfoxide (DMSO), polyethylene glycol (PEG) and chloroform. In the present work we have used different concentrations/ratio of solvents to solubilize and form a stable complex of drug with 99mTc-pertechnetate. Objective: The aim of the present study was to solubilize the drug using suitable solvent system, prepare the stable complexation with 99mTc and systematically evaluate physicochemical properties of 99mTc-glibenclamide complex. Materials and Methods: The GBD used for the labeling with 99mTc-pertechnetate was obtained from Micro Advanced Research Centre, Bangalore. To optimize the solubility of GBD we have used different ratio/concentration of the solvents such as PEG 400, ethanol and DMSO (1:1:1, 2:2:1 and 3:3:1). Different concentrations of (50 µg, 75 µg and 100 µg) of the SnCl2 .2H2O was added as a reducing agent in the preparation. Dissolved the required quantity of drug (5 mg) in the mixture of solvents (PEG 400, ethanol and DMSO) in 10 ml sterile glass vial. Add stannous chloride in the drug solution with vigorous stirring and used 10 mCi of freshly eluted 99mTc-sodium pertechnetate (0.1 to 0.2 ml). Heat the vial in boiling water bath (5 min, 10 min, 15 min and 20 min) for labeling of drug with 99mTc. Carried out the physicochemical evaluation of the labeled product (RCP was done in saline Rf = 0.1 and methanol Rf = 0.9). Stability of the drug solution (stored at 2-8 0C) has been evaluated for its labeling with 99mTc-sodium pertechnetate at different time points (15 days, 30 days and 60 days). Results and Discussion: The product formed clear solution when formulated with 3:3:1 of the PEG 400, ethanol and DMSO and lebeled efficiently using 75 µg of the SnCl2 .2H2O heated for 15 min. The pH of the product was found 5.0 (± 0.2) with RCP > 98 % (± 1.33) at 0 hr, 6 hr. The solubilized drug was found labeled with 99mTc-sodium pertechnetate efficiently for the period of 2 months without lyophilization. Conclusion: Labeling of GBD solution with 99mTc was found stable using optimum concentration of cosolvents without lyophilization. We can reduce the cost of the product by avoiding lyophilization.
Hepato 3: Comparison of therapeutic efficacy and toxicity profile of 90Y-SIRsphere and 188Re-N-DEDC lipiodol for treatment of inoperable hepatocellular carcinoma
Naresh Kumar, Shamim Ahmed Shamim, G. Shivanand, Shalimar, Sahil Jaswal, Himanshu Kumar Gupta
Department of Nuclear Medicine, AIIMS, New Delhi, India
Introduction: Trans-arterial radio-embolization (TARE) with 90Y-microspheres is a promising treatment option for inoperable HCC patients with multifocal lesions (BCLC-B) and malignant portal vein thrombosis (PVT) (BCLC-C). 188Re-N-DEDC lipiodol is an emerging TARE agent due to comparable β-energy (Eβmax 2.1 MeV) and penetration range (~11mm) of 188Re to 90Y. Indigenously developed TARE agent DEDC (Diethyl-dithiocarbamato) by BARC, Mumbai, labelled with 188Re in lipiodol phase has advantage of simple and on-site labelling procedure, cost-effectiveness. However, it has few post-treatment complications similar to TACE. Thus, present study aimed to compare the therapeutic efficacy and toxicity profile of 90Y-SIRsphere and 188Re-N-DEDC lipiodol for treatment of intermediate and/or advanced HCC. Materials and Methods: Radiologically and biochemically confirmed HCC patients with/without PVT having ECOG performance status ≤2 and Child Pugh score A/B were recruited. Baseline serum alpha-fetoprotein (S. AFP) was obtained for biochemical correlation and follow-up. The dosimetrically estimated activity was administered trans-arterially under fluoroscopic guidance through femoral branch in super-selective artery of tumor. Response was assessed initially at 3 months post-therapy by mRECIST criteria and S. AFP level. The clinical & biochemical toxicities were graded by CTCAE v5.0. Results: Twenty-four (24) patients (23 male; 1 female); 12 patients in each 90Y-SIRsphere and 188Re-N-DEDC lipiodol groups with comparable lesion size, mean age 57.5 ± 11.1 years were recruited for this study. Overall mean injected activity was 3.9 ± 1.9GBq for 90Y-SIRsphere group, and 4.1 ± 1.6GBq for 188Re-N-DEDC lipiodol group. Radiologically, in 90Y-SIRsphere group, 1 patient had complete or nearly complete response, 6 patients had partial response, 3 had stable disease while 2 had disease progression. In 188Re-N-DEDC group, 2 patients had complete response, 7 had partial response and 3 patients had stable disease. Biochemically, 5 patients (2 in 90Y-SIRsphere group and 3 in DEDC group) had non-AFP producing tumor. Thus, of 10 patients in 90Y-SIRsphere group, 2 had complete response and 5 showed partial response and 3 showed disease progression. Of 9 patients in DEDC group, 2 had complete response, 6 had partial response and 1 showed disease progression. All patients were available for toxicity evaluation. The post-therapy grade-1 clinical toxicities (Nausea, Vomiting, Fever, abdominal pain) were observed in 4/12 patients (~33%) in 90Y-SIRsphere group, and 6/12 patients (50%) in DEDC group for 2-3 days and were treated symptomatically. Grade 1 derangements in liver enzymes were seen in both group patients at 14 days follow-up lab investigation. None of the patient in either group had any pulmonary toxicity, myelosuppression or any other long term toxicity. Conclusion: TARE with 90Y-SIRsphere and 188Re-N-DEDC lipiodol shows almost similar response with very few toxicity in intermediate/advanced HCC patients.
Hepato 4: Design and development of an indigenous delivery system for direct delivery of 90Y-Glass microspheres (Bhabhasphere) in liver cancer patients
Anupam Mathur, B. K. Tiwary, Aaditya Shah, Amala Mathai, Arpit Mitra, N. C. Joseph, K. V. V. Nair, Anupam Mathur, Madhumita Goswami, Sudipta Chakraborty, Usha Pandey, Pradip Mukherjee
Department of Nuclear Medicine, Board of Radiation and Isotope Technology, Navi Mumbai, Maharashtra, India
Introduction: BRIT is involved in the production and supply of radiopharmaceuticals for healthcare applications. Recently, 90Y(Yttrium-90) labeled Glass Microspheres named “Bhabhasphere” for liver cancer therapy developed in BARC was commercialized from BRIT. For producing Bhabhasphere, 89Y Glass Microspheres (20-40 µm) are synthesized and irradiated in reactor. A delivery systemis required to be supplied with the productfor patient use. The delivery system is a mechanical system which slowly infuses the product into the cancerous liver under positive flow of saline. Development of such a system is challenging as the operation needs to be performed under sterile conditions on a radioactive preparation. Bhabhasphereconsists ofheavyglass particles which impose resistance during transit through delivery assembly. Also, the size of infusion catheter connected to liver artery exerts back pressure resisting the forward flow of Bhabhasphere. Considering all the above factors, BRIT has indigenously developed a delivery system for use with Bhabhasphere. Materials and Methods: Figure 1 is the sketch of Bhabhasphere Delivery system, a Perspex based set-upwhichhas required shieldingand securely encloses the product vial. The vial holder in the Perspex assembly is designed to hold a V-shapedglass vial, the latter ensuring complete transfer of radioactive material. The vial cap was made frompolyether ether ketone (PEEK)along with ferrule fittings to prevent any leak or pressure release from top of the vial during product infusion. The sterile pre-assembled tubing inside Perspex set-up is a three-way tubing lineintegratedon amedical grade three way stop-cock for secured delivery of product inside the cancerous liver. One end of the stop-cock was connected to a sterile saline bottle, the second end to a syringe for saline withdrawal and the third end to the patient catheter (via radioactive dose vial). There were few one-way check valves used in tubing to regulate the unidirectional saline and product flow and 18 G spinal needles were used to pierce the radioactive dose vial to effect smooth infusion of Bhabhasphere through them. Results and Conclusion: Bhabhasphere delivery system was rigorously tested and used in a single patient treatment with 4.625 GBq (125 mCi) of Bhabhasphere. The system performed satisfactorily where > 90% of Bhabhaspherecould be infused in cancerous liver of a patient. The bremsstrahlung SPECT images post-infusion indicated uniform activity distribution in cancerous liver and patient showed relief over time. Efforts are underway to further optimize the size of the assembly and for minimizing the man Rem exposure to the nuclear medicine technicians.

Hepato 5: Gastric emptying patterns in diabetic gastroparesis patients: insights from a scintigraphy-based study at AIIMS Rishikesh
Nikhil Gupta, L. S. Sanjith, Vandana Dhingra, Shranav Jha, S. Abhilash, K. Vidhya, Sanisetty Sarath
Department of Nuclear Medicine, AIIMS, Rishikeah, Uttarakhand, India
Introduction: Diabetes Mellitus (DM) is a chronic metabolic disorder characterized by elevated blood sugar levels. One of its complications, diabetic autonomic neuropathy, can impact various bodily systems, including the gastrointestinal system. Gastroparesis, characterized by delayed gastric emptying, is a common symptom of diabetic autonomic neuropathy. While extensive research on overall gastric emptying exists, there is a gap in understanding compartmental gastric emptying patterns. This study aims to describe distinct gastric emptying patterns in Type 2 DM patients with gastroparesis symptoms, providing valuable insights for targeted management. Materials and Methods: Gastric emptying scintigraphy was conducted using a standardized radioactive idly (savoury cake) meal. Patients were screened based on HbA1c levels and fasting blood glucose, ensuring they were below 275 mg/dL. Symptom severity was assessed using the Gastroparesis Cardinal Symptom Index (GCSI) score. Scintigraphy was performed after an overnight or minimum six-hour fast. Images were acquired using a dual-headed gamma camera, and manual areas of interest (ROI) were marked on anterior and posterior images at different time intervals (0 and 30 minutes, 1, 2, 3, and 4 hours). Gastric retention percentages were calculated and compared with normal values. Gastric retention patterns and tracer distribution were visually evaluated. Results: The study included 68 Type 2 DM patients with gastroparesis symptoms, predominantly in the 51-60 age group(average age: 52.61 years), with a majority being females. The average diabetes duration was 9.47 years, with mean fasting blood glucose and HbA1c levels of 151.49 mg/dL and 8.99%, respectively. Most participants exhibited moderate symptom severity (GCSI score ≤18). Seven gastric emptying patterns were identified: normal, fundic incompliance, abnormal distribution, antral dysmotility, reduced gastric volume, gastric hurrying, and gastroesophageal reflux. Gastric hurrying was the most prevalent(30%), followed by abnormal distribution(23.5%) and normal patterns(22.1%). Half of the participants had normal gastric emptying times, while 30.9% experienced rapid and 19.1% experienced delayed emptying. Gender was significantly associated with emptying time, with females more likely to have normal emptying times and males more likely to have rapid or delayed emptying. Longer diabetes duration was associated with delayed emptying. However, no significant associations were found between age, fasting blood glucose, HbA1c, and emptying time. A weak positive correlation existed between GCSI score and half-life, but no significant correlation was observed between GCSI score and retention at 4 hours. Conclusion: This study sheds light on diverse gastric emptying patterns in Type 2 DM patients with gastroparesis symptoms. Gastric hurrying emerged as the most common pattern, indicating rapid gastric emptying. Importantly, this study found no significant relationship between these patterns and gastric emptying times. Furthermore, it highlighted the possibility of dumping syndrome in patients with rapid gastric emptying and gastroparesis symptoms, emphasizing the need for tailored management approaches for impaired fundic accommodation and antral dysmotility. These findings underscore the utility of gastric emptying scintigraphy as a valuable tool for evaluating gastric motility disorders in Type 2 DM patients, facilitating the development of precise treatments for specific gastric motility issues.
Hepato 6: Comparison of functional liver volumes using Tc-99m sulfur colloid SPECT/CT and standard liver volume formula
Sikandar Saini, S. S. Prashar, S. Saini, A. Bhattacharya, B. R. Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: Functional liver volume (FLV) estimation is an important determinant for safe hepatectomy. Common diseases affecting liver function include non-cirrhotic portal fibrosis (NCPF) and liver cirrhosis (LC). Accurate assessment of liver function is essential to effectively manage these patients. In this study, Tc-99m Sulfur colloid SPECT/CT was used to evaluate FLV, which was compared with standard liver volume (SLV) estimated using Chandramohan's formula. Materials and Methods: The study was performed in 24 patients with NCPF (n = 12) and LC (n = 12) referred to our department from the department of Hepatology at PGIMER, Chandigarh, for routine liver imaging. Tc-99m sulfur colloid liver scan was acquired 30 minutes after intravenous administration of 3mCi of radiotracer. Eight static (anterior, posterior, right anterior oblique, left anterior oblique, right posterior oblique, left posterior oblique, right lateral, left lateral) planar images in 128×128 matrix were acquired for 2 minutes each under a dual head SPECT/CT system (Symbia-T16, Siemens, Germany) with low energy high resolution collimator. SPECT of the liver was also obtained in 64×64 matrix (32 views) with CT (100mA,120 KVp). Images were reconstructed using Flash-3D algorithm. Reconstructed images were analyzed using 3D volumetric analysis software. Regions of interest were drawn on the trans-axial slices using a fixed threshold (40%) iso-contouring method to calculate FLV. The SLV was calculated using Chandramohan's formula (243 + [186xBSA] + [11.4xBW]). Data was then assessed using linear regression. Results: The liver showed adequate homogenous tracer uptake in NCPF and impaired heterogenous tracer uptake in LC patients. Mean FLV was 933.7 ± 365.2 ml and mean SLV using Chandramohan's formula was 1183.2 ± 209.8 ml in the entire cohort of 24 patients. Mean FLV was 1022.5 ± 424 ml and 844.9 ± 286.2 ml in NCPF and LC patients respectively. Mean SLV was 1200.1 ± 216.4 ml and 1166.3 ± 211.2 ml in NCPF and LC patients respectively. Analysis of SPECT FLV as a function of SLV demonstrates a statistically significant linear correlation (r2 = 0.373). The SPECT FLV is approximately 21.1% less than the volume obtained from Chandramohan's formula. In LC patients, SPECT FLV as a function of SLV demonstrates a statistically significant linear correlation (r2 = 0.328). SLV is overestimated in NCPF and LC by 14.8% and 27.56% respectively. Conclusion: Our study confirms a difference in volume from the two methods with SPECT volume lower than volume estimated by Chandramohan's formula. Our findings highlight the potential of Tc-99m sulfur colloid SPECT/CT to diagnose and monitor FLV in different disease conditions, with distinct differences in FLV observed in these groups. This non-invasive approach could aid in treatment planning and assessing disease progression, particularly in cirrhotic patients where FLV reduction correlates with disease severity.
Hepato 7: Image based quantification method for non-invasive diagnosis of Sphincter of Oddi dysfunction using hepatobiliary scintigraphy
Komalpreet Kaur, Piyush Aggarwal, Bhagwant Rai Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: Non-invasive diagnosis of Sphincter of Oddi dysfunction (SOD) in patients with post-cholecystectomy pain syndrome is difficult. Hepatobiliary scintigraphy plays an important role in diagnosis but is limited due to the complexity of processing data into meaningful results. Currently, positive and negative results for SOD are reported based on the Scintigraphic Score (SS) i.e., Sostre score. Aim of the study was to evaluate the usefulness of dynamic imaging and composite image processing software (Oasis software) in identifying SOD. Materials and Methods: This retrospective study included data of 34 patients (30 F:4 M, mean age 40 ± 8 years and age range 23-67 years) referred for SOD evaluation. All the patients were subjected to dynamic hepatobiliary scintigraphy, performed with 99mTc-HIDA for 60 minutes without any stimulation. The final scan reporting in all patients was done on the basis of Sostre score. The acquired data was also processed and analysed manually as well as using SOD analysis software from Oasis. Regions of interests (ROI) were drawn around the right liver lobe (RLL) and common bile duct (CBD) to generate a Time-Activity-Curve (TAC). Quantitative parameters such as the percent of CBD emptying, CBD (60)/Liver (60) Ratio and CBD (60)/Liver (15) Ratio were analysed. Results: The scans were reported SOD positive and negative on the basis of Sostre score. Optimal cut-off value for the percent of CBD emptying, CBD (60)/Liver (60) Ratio and CBD (60)/Liver (15) Ratio were calculated by receiver operating characteristic (ROC) analysis. The results demonstrated that the % CBD emptying had the optimal cut-off value of 21.65 (AUC: 0.870; p < 0.01), which yielded a sensitivity of 85% and a specificity of 78.6% for the detection and exclusion of SOD, respectively. Similarly, we found CBD (60)/Liver (60) Ratio cut-off threshold of 1.15, with a sensitivity of 68.8% and specificity of 61.1% for SOD (AUC: 0.549; p < 0.01) and CBD (60)/Liver (15) Ratio cut-off threshold of 1.55, with a sensitivity of 68.8% and specificity of 50.0% for SOD (AUC: 0.623; p < 0.01). Low dose SPECT-CT was done in few cases to determine the most precise borders of the CBD and RLL. Conclusion: Hepatobiliary scintigraphy may become the initial non-invasive investigation in the diagnosis of SOD, with SO manometry being reserved for uncertain cases. The above quantitative imaging method and the % CBD emptying threshold value can be used to identify SOD objectively with a high likelihood of stratifying future patients into (-) and (+) SOD categories. This imaging criteria can supplement or replace Sostre score, however, larger sample size is required for confirming the results in further studies.
Hepato 8: Intra-arterial PRRT with Lu-177 DOTATATE in liver-dominant metastatic neuroendocrinetumors: Early assessment of efficacy and toxicity
Indraja Dev, Venkatesh Rangarajan, Ameya Puranik, Nilendu Purandare, Sneha Shah, Archi Agrawal, Sayak Choudhury, Suchismita Ghosh
Department of Nuclear Medicine, ACTREC, Tata Memorial Center, Mumbai, Maharashtra, India
Introduction: PRRT with Intravenous Lutetium 177 DOTATATE is the recommended first line treatment for locally advanced/metastatic Gastroentero-pancreatic Neuroendocrine tumors. Its therapeutic potential and impact on Progression free survival was well established in NETTER 1 trial. In the post hoc analysis, it was observed that liver dominant bulky disease is associated with poor outcomes even after IV PRRT. One of the major principles of Theranostics is that absorbed dose by the tumor depends on the route of administration and dose delivered. Few retrospective studies have documented the efficacy and safety of intra-arterial PRRT over intravenous. Currently ongoing LUTIA trial is evaluating the incremental benefit of intra-arterial administration of PRRT over intravenous route with intra-individual randomization. We proposed to administer Lu-177-DOTATATE in intra-arterial mode for higher first pass localisation to somatostatin receptors, higher residence time in liver metastases and more cytotoxic effect of radiation to tumor. This study aimed at assessing early hematological, renal and hepatotoxicity and objective response to intra-arterial PRRT (IA PRRT). Materials and Methods: 14 patients (4 female, 10male), were prospectively assessed. 5/14 underwent 2 cycles whereas 3/14 underwent 3cycles, and 6/14 received 1 cycle of IA PRRT. 200 mCi of Lu-177-DOTATATE was administered in 15-20 minutes by IA route under angiographic guidance. Patients were asked to follow up at 4and 8 weeks with hematological, liver and renal functional parameters, and Ga-68 DOTATATEPET/CT after 8 weeks. Response was assessed using RECIST 1.1 and EORTC PET criteria. Results: Safety: 2/14 patients had high total and direct bilirubin, which reverted to normal after IA PRRT. 3 patients had low albumin, which improved after 1 cycle. 9 patients showed no worsening of liver function. 2 patients showed grade 1 hematotoxicity, which reverted to normal.5 patients showed high creatinine, but preserved GFR and EC clearance. On follow up at 8 weeks, serum creatinine reverted to normal. Efficacy: In 5 patients who underwent 2 cycles of IA PRRT, 3 showed partial response (PR) on RECIST 1.1 and partial metabolic response(PMR) on EORTC criteria, whereas 2 showed stable disease (SD). In patients who underwent 3 cycles, 1 showed SD, whereas other patient showed PMR on DOTANOC PET/CT, with PR in size. Amongst the remaining 7 patients, 5 showed PMR, whereas the other 2 showed SD. Thus9/14 patients showed PR whereas 5 showed SD on metabolic and size criteria. Conclusion: Our study with its encouraging results, with respect to safety and efficacy has generated good evidence for for recommending IA PRRT as standard of care for large sized liver-dominant metastatic NETs.
Hepato 9: [177Lu]Lu-PSMA-617 radioligand therapy in mCRPC patients with liver metastases: A therapeutic conundrum
S Satapathy, A. Sood, M. P. Yadav1, S. Ballal1, K. R. Chandekar, P. Aggarwal, R. K. Sahoo1, C. K. Das, B. R. Mittal, C. S. Bal1
Department of Nuclear Medicine, PGIMER, Chandigarh, 1Department of Nuclear Medicine, AIIMS, New Delhi, India
Introduction: [177Lu]Lu-PSMA-617 radioligand therapy has gained prominence as a viable therapeutic strategy for patients with end-stage metastatic castration-resistant prostate cancer (mCRPC). The presence of liver metastases has been linked to an adverse prognosis in mCRPC patients. However, exclusive data concerning the efficacy and safety of [177Lu]Lu-PSMA-617 in mCRPC patients with liver metastases remains limited. In this study, we report our institutional experience with [177Lu]Lu-PSMA-617 in this specific cohort. Materials and Methods: Data of consecutive patients of mCRPC with documented liver metastases and treated with [177Lu]Lu-PSMA-617 at our centres, from 2015 to 2022, were collected and retrospectively analysed. The various outcome measures included: best PSA response rate (PSA-RR) (defined as proportion of patients achieving a ≥50% decline in PSA from baseline); objective radiographic response rate (ORR) (defined as proportion of patients achieving a complete or partial radiographic response); radiographic progression-free survival (rPFS) (time from first cycle till documented radiographic progression or death due to any cause); overall survival (OS) (time from first cycle till death due to any cause); and adverse events (evaluated as per the Common Terminology Criteria for Adverse Events, version 5.0). Results: Eighteen males (median age: 70 years, range: 59-85) with mCRPC and documented liver metastases on [68Ga]Ga-PSMA-11 PET/CT were included in this analysis. Of these, five (27.8%) patients had solitary liver metastases while the rest had multiple liver lesions. Additionally, 10/18 (55.6%) patients had distant lymph nodal metastases, 17/18 (94.4%) patients had skeletal lesions; and 6/18 (33.3%) patients had lung involvement. Prior systemic treatments in the metastatic setting included: docetaxel (13 patients, 72.2%); abiraterone (13 patients, 72.2%), enzalutamide (8 patients, 44.4%), and cabazitaxel (2 patients, 11.1%). The patients received a median cumulative activity of 11.1 GBq (range: 3.7-37 GBq) of [177Lu]Lu-PSMA-617 over 1-7 cycles at 8-12 weeks intervals. Two patients were lost to follow-up after the first cycle. A PSA decline of ≥50% from baseline was achieved in 4/16 (25%) patients (best PSA-RR). Fourteen patients underwent radiographic follow-up with the ORR being 4/14 (28.6%). The median PFS was 11.0 months (95% CI: 6.1-11.9), while the median OS was 13.0 months (95% CI: 11.5-14.5). Grade 3 anemia was the only major adverse event noted in 2/18 (11.1%) patients. Conclusion: Despite an adverse prognosis, [177Lu]Lu-PSMA-617 is safe and has acceptable efficacy in the treatment of mCRPC with liver metastases. Limited response rates can be attributed to the neuroendocrine transdifferentiation in such lesions, leading to relatively low PSMA expression. Nevertheless, the presence of liver metastases should not preclude patients from receiving [177Lu]Lu-PSMA-617 radioligand therapy. Optimizing patient selection using a stricter eligibility criterion (e.g. treating lesions with PSMA expression 1.5-2 times that of normal liver), and dual [68Ga]Ga-PSMA-11/ 2-[18F]FDG PET/CT can potentially lead to better outcomes.
Hepato 10: Multimodality treatment of advanced hepatocellular carcinoma: A novel strategy for treating hepatocellular carcinoma with portovenous tumour thrombus
Mrinalini Koley, P. Thakral, S. S. Das, D. Malik J. Gupta, Jyotsna, N. Singh, N. Rana, I. B. Sen
Department of Nuclear Medicine, FMRI, Gurugram, Haryana, India
Introduction: Portal vein tumor thrombosis (PVTT) is the most common macrovascular invasion of HCC and occurs in about 35%-50% of patients. PVTT represents a strong negative prognostic factor and is associated with impaired hepatic reserves leading to reduced tolerance. One of the strategies adopted as part of the multimodality management of patients of advanced HCC with PVTT by the multispecialty liver cancer management group at our institute is the combination of selective intra-arterial radioembolisation (SIRT) with resin spheres loaded with 90Yttrium (SIR-Spheres®; Sirtex Medical, Sydney, Australia) followed by SBRT directed towards the PVTT combined with systemic therapy with Lenvatinib. The SIRT and SBRT provide locoregional control while Lenvatinib provides systemic control. The authors here present their early experience using triple modalities sequentially, SIRT with Y90 Resin spheres followed by SBRT towards PVTT and systemic therapy with Lenvatinib, in 20 patients of advanced HCC with PVTT. Materials and Methods: 20 patients of unresectable HCC with PVTT underwent sequential SIRT with 90Y-SIR Spheres followed by SBRT to PVTT and Lenvatinib therapy. Median age of patients was 63 years. Dose of 90Y SIR-Spheres® was based on the partition model of dosimetry with a tumour dose of at least 150 Gy. The mean prescribed dose of EBRT was 49.7 Gy (range: 48-55 Gy) in 3-5 fractions. A clinical evaluation and laboratory testing, was performed for all patients at the end of the first month after treatment, then at 3-month intervals thereafter. Serum liver function tests, Child-Turcotte-Pugh score (CTP) and Serum Alpha Feto Protein (AFP) were obtained pre-SIRT (baseline) and 2, 4, and 8 weeks after EBRT treatment. An image study was usually performed every 3 months. The mRECIST guideline was applied for response evaluation. Results: Mean change drop in Serum AFP levels was 85.86% with 90% patients showing ORR. The estimated median survival by Kaplan-Meir Method was 18 months with 42% patients alive at the end of the study. None of the patients developed developed > grade 2 liver toxicities assessed by NCI Common CTCAE version 5.0. Conclusion: The treatment produces high objective response rate and good overall survival and is safe with no CTCAE grade 3/4 toxicities seen. Larger studies are needed to validate the results of this small study, the initial experiences are very encouraging.
| Parameter | LBR 5 min | LKR 5 min | LBR 30 min | LKR 30 min | LBR 1 h | LKR 1 h | LBR 24 h | LKR 24 h |
|---|---|---|---|---|---|---|---|---|
| BA | 1.27±0.73 | 2.6±1.3 | 2.5±1.1 | 4.7±2.2 | 2.7±1.36 | 4.4±1.9 | 3.8±1.5 | 3.98±1.39 |
| NH | 1.62±0.43 | 3.7±1.1 | 3.0±0.79 | 5.3±2.3 | 3.25±0.88 | 6.0±2.9 | 5.9±2.3 | 5.6±2.29 |
| P | 0.132 | 0.021* | 0.149 | 0.416 | 0.211 | 0.055 | 0.003* | 0.014* |
BA: Biliary atresia, NH: Neonatal hepatitis, LBR: Liver: blood pool ratio, LKR: Liver: kidney ratio
Hepato 11: Establishment of the reference value of gall bladder ejection fraction using a fatty meal protocol in Indian population by performing hepatobiliary scintigraphy
Ashutosh Kumar, Naresh Kumar, Priyanka Gupta, Khangembam Bangkim Chandra, Chetan D. Patel, Rakesh Kumar
Department of Nuclear Medicine, AIIMS, New Delhi, India
Introduction: Hepatobiliary scintigraphy is a diagnostic nuclear medicine procedure to evaluate the biliary system that is used to quantify gall bladder ejection fraction (GBEF) with 99mTC-Mebrofenin. Stimulated hepatobiliary scintigraphy using cholecystokinin (CCK) has been considered as the gold standard method for assessing gall bladder function. However fatty meal was found to be a good alternative to CCK in hepatobiliary scintigraphy GBEF measurement. Yet, there are no reference values for fatty meal in Indian population. Thus, the present study aimed to assess the reference values of GBEF with fatty meals in Indian population. Materials and Methods: Hepatobiliary scintigraphy will be performed on a gamma camera fixed with LEHR collimator after the intravenous administration of 5 mCi of 99mTc-Mebrofenin. Pre-meal multiple static images for 2 min. each will be acquired at different time points (30, 45, 60 min as required). The image with highest gall bladder activity concentration and minimal liver activity would be taken as the reference image. A standard fatty meal consisting of 40 grams of butter and two slices of bread would then be consumed by the subjects within 5 minutes followed by ~100 mL of water. Post-meal multiple static images will be acquired for 2 min each at 30, 45, 60 minutes after the completion of meal. For GBEF, the regions of interests (ROIs) would be delineated over the gall bladder and background liver in the right lobe. Decay corrected counts would then be generated. From these counts, gallbladder ejection fraction (GBEF) would be generated for 30, 45 and 60 minutes post-meal. Results: Eleven (11) healthy volunteers (4 male; 7 female) having mean age of 47.1 ± 9.1 years were recruited for the study. The mean % GBEF at 30 min, 45 min, and 60 min. were found to be 34 ± 0.19%, 35 ± 0.24% and 38 ± 0.23%, respectively. The highest gall bladder activity concentration with minimal liver activity in pre-meal multiple static images was found at 60 minutes imaging time point. Thus, the reference values for post-meal % GBEF was considered for 60 min. imaging time point. So, the reference value of % GBEF was 38 ± 0.23%. Conclusion: The reference value of % GBEF in Indian population has been established as 38 ± 0.23 %, at 60 minutes post-meal time point. A value lower than the above-mentioned cut-off may be regarded abnormality in gall bladder/liver/biliary tract in Indian population.
Hepato 12: Semiquantitative parameters on hepatobiliary scintigraphy to differentiate biliary atresia and neonatal hepatitis in patients with no identifiable biliary to bowel transit
Tejasvini Singhal, Girish Kumar Parida, Parneet Singh, Sai Sradha Patro, Krishna Mohan Gulla, Kanhaiyalal Agrawal
Department of Nuclear Medicine, AIIMS, Bhubaneswar, Odisha, India
Introduction: The two most prevalent causes of neonatal cholestasis are biliary atresia(BA) and neonatal hepatitis(NH). These conditions have distinct etiologies, management, and prognoses. BA is considered a surgical emergency, whereas NH typically requires conservative treatment. Therefore, distinguishing between these conditions is of paramount importance. Current gold standard for imaging to rule out EHBA is hepatobiliary scintigraphy(HBS), which involves visually assessing the tracer's appearance in the bowel. However, in cases where hepatic function is impaired, biliary-to-bowel transit may not be observable, even in NH cases. This study aims to assess the diagnostic efficacy of semi-quantitative parameters on HBS to distinguish BA and NH when there is a lack of biliary-to-bowel transit for up to 24 hours. Materials and Methods: The study involved retrospective analysis of 35 patients less than 3 months of age with diagnosis of neonatal cholestasis where HBS failed to differentiate BA and NH. Histopathological examination was taken as the gold standard. Semiquantitative parameters calculated include: Liver: blood pool (LBR) and liver: kidney ratios (LKR) at 5 minutes, 30 minutes, 1 hour and 24 hours. Mean values for the two groups were calculated. Student's t-test was employed to assess the statistical significance of difference of mean between the two groups. ROC curve was also drawn to determine a cut-off of these ratios to differentiate between the two groups. Results: The study included 35 patients (24 males) with a median age of 2 months (range: 24 days to 3.5 months). Of these, 23 patients had a diagnosis of BA while 12 had NH. Mean semi-quantitative parameters in the two groups are given in Table 1. Mean LBR and LKR at 24 hours were statistically different in the two groups (p-value <0.05). Receiver operating characteristic (ROC) curve analyses showed highest AUC for LBR at 24 hr 0.790 (CI:0.624-0.955, p-value 0.005) and LKR at 24 hr - 0.783 (CI: 0.620-0.945, p-value:0.007). For diagnosis of BA a cut-off value of <3.65 for LBR at 24 hours (sensitivity and specificity of 73.9% and 75% respectively) and < 4.64 for LKR at 24 hours (sensitivity and specificity of 69.6% and 83.3% respectively) were found to be pertinent. Conclusions: HBS serves as non-invasive gold standard to rule out EHBA. Semi-quantitative indices LBR and LKR at the 24-hour can accurately differentiate between EHBA and NH even in cases with compromised hepatic function where traditional visual interpretation of tracer transit proves inadequate. Further research is warranted to establish the broader applicability of these semi-quantitative parameters in clinical practice.
Category: Infection and Inflammation
Infection 1: Dosimetry and long term therapeutic efficacy of 177Lu-tin colloid radio-synovectomy in patients with inflammatory knee joints conditions, refractory to conventional therapies
Naresh Kumar, Shamim Ahmed Shamim, Sahil Jaswal, Himanshu Kumar Gupta, Geetanjali Arora, Ravi Mittal, Mohd. Tahir Ansari, Ranjan Gupta
Department of Nuclear Medicine, AIIMS, New Delhi, India
Introduction: Radiosynovectomy (RSV) uses the radionuclide loaded colloidal particles such as 177Lu-tin-colloid which are rapidly phagocytized by macrophages in the inflamed synovial membrane that leads to the reduction in the synovial inflammation. Our previous experience with 177Lu-tin colloid RSV in inflammatory arthritic patients were encouraging, however it was limited to intraarticular injection of empirical activity in small patient group and had less follow-up time. Thus, present study is aimed to assess the long-term therapeutic efficacy with intra-articular administration of dosimetrically estimated 177Lu-tin-colloid RSV in patients with chronic inflammatory knee joint conditions, refractory to conventional treatment. Materials and Methods: 177Lu-tin-colloid were prepared by the methodology previously published by our group Arora G. et al. Dosimetry of 177Lu-tin-colloid was adapted by absorbed dose profile given by Torres M. et al. Considering the S-Values (Gy/MBq*h) for 250 cm2 synovium area, 0.02 cm thickness of synovial lining cells, and assuming the complete radionuclide decays in the knee joint, the 90Y-dose equivalent therapeutic activity of 177Lu-tin colloid was estimated by varying the prescribed absorbed dose with severity of disease and administered intra-articularly to the inflamed knee joint. Blood pool bone scan and clinical parameters e.g. mobility score (0-3), pain score (0-10), analgesic score (0-6), tenderness score (0-3) and joint swelling score (0-3) were performed at baseline, 6, 12 and 24 month from RSV. The patients with > 50% decrease in the cumulative scores of clinical parameters from baseline and a return of blood pool activity to background (thigh) level were considered as responders to therapy. Results: A total of 62 knee joints in 58 patients with various inflammatory joints conditions like rheumatoid arthritis (24 joints), pigmented villonodular synovitis (12 joints), Hemophillic arthritis (9 joints), lipoma arborescens (5 joints), non-specific chronic synovitis (7 joints), spondyloarthritis (4 joints), psoriatic arthritis (1 joint), who were refractory to conventional therapy underwent intra-articular injection of dosimetrically estimated activity 1750-2220 MBq of 177Lu-tin-colloid to inflamed knee joint. Of 62 inflammatory knee joints, 48 joints (~77%) were considered as responder and 14 (~23%) as non-responders at 6-months. Of 48 joints, remission were seen in 41 joints (~85%), while 7 (~15%) had recurrences at 1 year duration. Further, long term follow-up at 2-years, 35 (~73%) had complete remission and 13 (~27%) had recurrence. There was significant reduction in blood pool activity as well as change in cumulative score of clinical parameters at 6, 12 and 24 months when compared with baseline (p < 0.05). No lymphedema, infection, radio-necrosis, or any other serious adverse effects were observed in any patient. Conclusion: Dosimetrically administered therapeutic activity of 177Lu-tin colloid RSV is useful treatment modality for long-term remission in patients of chronic inflammatory joints, refractory to conventional treatment.
Infection 2: FDG PET/CT patterns in the pharynx in oncologic patients with asymptomatic (omicron) SARS-CoV2 infection: Can we distinguish from recurrent/metastatic disease? The New York experience
Reema Goel, Marc Berns, Rahman Akinlusi, Munir Ghesani
Department of Diagnostic, Molecular and Interventional Radiology, Mount Sinai Hospital, New York, USA
Introduction: The omicron variant of SARS-CoV-2 seems to principally involve the upper aerodigestive tract, with prominent, symmetric FDG uptake throughout the nasopharynx, oropharynx, and tonsils (Waldeyer's ring) with or without associated FDG-avid upper cervical lymphadenopathy. These findings can be confounding on PET/CT imaging where it can be misinterpreted for either local recurrence of head/neck cancer or metastatic spread of disease. In this study we attempt to identify the relationship between COVID-19 Omicron/ other COVID variants and subsequent findings on PET/CT to better elucidate the expected patterns of FDG uptake for this entity as well as to differentiate this pattern of FDG uptake from recurrent head and neck cancers, and metastasis/lymphoma. Materials and Methods: We retrospectively analyzed PET/CTs performed for evaluation of cancer in the Mount Sinai Health System between November 1, 2021 and March 3, 2022. Inclusion criteria included all patients who had a positive COVID-19 test within 40 days of the PET/CT examination as well as indication for PET-CT imaging for initial staging, follow-up or monitoring of the treatment response for various cancers. None of these patients were symptomatic for acute respiratory illness. 95 patients (age range 24-84 years; 41 males, 54 females) were finally included. We analyzed pattern of uptake/SUV values in the Waldeyer's ring, cervical lymphadenopathy and degree of ground glass opacities (GGOs) in the lungs. Results: Suspicious metabolic findings in the pharynx comprising of increased FDG avidity in the nasopharynx and/or Waldeyer's ring, with and without cervical lymphadenopathy were seen in 27/95 (28.4%), 15/95 (15.8%) and 12/95 (12.6%) patients respectively. The range of SUV max in the Waldeyer's ring was 2.1-10.7. Additionally, 19/27 (70%) patients had FDG avid GGOs in the lungs with 2/19 showing severe degree of lung involvement classified as grade 3, and 17/19 showing grade 1 and 2 lung involvement. 6/22 patients with lymphoma had FDG avidity in the Waldeyer's ring without any cervical lymphadenopathy, however 4/22 patients with lymphoma had cervical nodes (2/4 with nonenlarged mildly FDG avid nodes without prior involvement by lymphoma deemed reactive/infective and 2/4 with decreasing size of nodal lymphoma compatible with treatment response, who also had no FDG avidity in the Waldeyer's ring). Only 1/6 patients with head and neck squamous cell cancers had increased FDG avidity in the Waldeyer's ring as well as FDG avid bilateral upper cervical lymph nodes and needed biopsy confirmation to rule out recurrent disease. Conclusion: SARS-CoV-2 viral infection in asymptomatic PET-CT cancer patients with Omicron variant shows suspicious metabolic findings with varying FDG avidity in the upper aerodigestive tract with or without cervical lymphadenopathy in up to 30% of patients. Majority of these patients also show mild to moderate degree of lung involvement. It represents a challenging scenario both for the diagnosis and also regarding the epidemiologic context, especially with Omicron variant. However, we rarely needed an invasive approach to distinguish infection from recurrent malignancy or metastases in our patient population.
Infection 3: Comparison of contrast enhanced computed tomography and F18-fluorodeoxyglucose positron emission tomography/computed tomography in the detection of residual or recurrent disease in patients of mucormycosis after surgical debridement
Ankita Phulia, Ishwar Singh, Shobhana Raju, Bangkim Chandra Khangembam, Rakesh Kumar
Maulana Azad Medical College, New Delhi, India
Introduction: There was a steep rise in the cases of mucormycosis especially in COVID-19 patients who were diabetic and were treated with corticosteroids injudiciously. Rhinocerebral (black fungus) is the most common and the most life-threatening form of mucormycosis, usually seen in patients with uncontrolled diabetes. Most of these patients present with orbital/facial pain, swelling, ptosis and followed by loss of vision. CECT and/or MRI remain the imaging modalities choice for accurate delineation of disease extent. However, CECT/MRI have limited sensitivity in the detection of residual or recurrent disease after surgery as normal anatomy is distorted and thereby, cannot differentiate residual/recurrent disease from post-treatment fibrosis. FDG PET/CT being a functional/metabolic imaging may be useful to overcome these limitations of CECT/MRI. The present study was aimed to compare the efficacies of CECT and FDG PET-CT in the detection of residual or recurrent disease in patients of rhino-orbito-cerebral mucormycosis after surgical debridement. Materials and Methods: It was a prospective observational study conducted from July 2022 – September 2023. A total of 33 mucormycosis patients who have already undergone surgical debridement and now presenting with clinical suspicion of residual or recurrent disease were included in this study. There were 29 male and 4 female patients. The mean age was 53.27 ± 10.97 with age range 24 – 74 years. The mean time between the initial surgical treatment and suspected recurrence was 49.28 ± 55.27 days (range 28 – 240 days). All patients underwent CECT as the initial modality after surgery. MRI was reserved for patients with orbital apex and intracranial involvement. All patients also underwent PET-CT after intravenous injection of 10 mCi of FDG. PET/CT images were looked for areas of abnormal FDG uptake which is defined as increased FDG uptake compared to the adjacent region and/or physiological uptake of the liver. Regions of interest (ROI) were drawn around the area of abnormal uptake for measurement of semi-quantitative parameters such as standardized uptake value (SUV). All patients with abnormal CECT and/or PET/CT results underwent a KOH swab or biopsy for confirmation of the diagnosis. In cases where a KOH swab or biopsy could not be done or in cases of equivocal results, patients were assessed using clinical and/or imaging follow-up. Results: Of 33 patients, PET/CT had 21(64%) positive and 12 (36%) negative for residual/recurrent disease. Mean of SUVmax of the positive lesions was7.22 ± 3.05. Both PET-CT and CECT/MRI were concordant in 25 patients and discordant in 8 patients. On the basis of the final diagnosis of patients, PET-CT had a sensitivity of 100%, specificity of 92%, PPV of 95%, NPV of 100% and accuracy of 97%. CECT/MRI found to have sensitivity of 90%, specificity of 54%, PPV of 75%, NPV of 78% and accuracy of 76% in these patients. PET/CT showed a higher diagnostic value when compared with CECT/MRI. Conclusion: F18 FDG PET-CT was found to be useful for the accurate detection of residual or recurrent disease after surgery and was superior to CECT/MRI. FDG PET-CT can be a valuable tool in the future to guide optimal patient management which can be either related to antifungal treatment or surgical re-intervention.
Acknowledgement: STS ICMR (ID 2022-01062) Approved Project for MBBS Student.
Infection 4: Role of triple phase bone scan in evaluation of skull base osteomyelitis: A retrospective case series done at AIIMS Rishikesh
Nikhil Gupta, Shranav Jha, Vandana Dhingra, L. S. Sanjith, K. Vidhya, S. Abhilash
Department of Nuclear Medicine, AIIMS, Rishikesh, Uttarakhand, India
Introduction: Skull base osteomyelitis (SBO) is a relatively uncommon condition that typically develops as a result of untreated infection of the temporal bone region that extends inferiorly to the infratemporal fossa, most frequently as a result of necrotizing external otitis brought on by Pseudomonas aeruginosa in a diabetic patient. It can be difficult to diagnose, however the following factors all contribute to the diagnosis of SBO: clinical characteristics, radiologic signs of infection, negative results from a biopsy for malignancy, and positive results from microbiologic tests. In addition to CT and MRI, bone scans (BS) are helpful for reliably detecting bone infection. Materials and Methods: Retrospective records review of 10 patients with probable SBO was conducted. After an intravenous tracer injection, a triple phase BS (dynamic flow followed by static blood-pool and 3 hour delayed imaging) and SPECT/CT of the skull were conducted (Tc-99m MDP). Results were compared to those from clinical, laboratory, diagnostic CT, and MRI scans. Results: Eight of the ten cases were men and two were women. The mean age was 62.8 years, with a range of 40 to 80. Six out of ten patients had hypertension, and all had diabetes. The most frequent initial complaint was ear discharge (8/10), followed by fever (6/10), whereas facial nerve palsy and diplopia were observed in 4/10 and 2/10 individuals, respectively. Microbiological culture of ear discharge from 8 out of 10 patients revealed Pseudomonas aeruginosa as the cause; 2 of the 8 patients with Pseudomonas aetiology had mixed infections, 1 with Methicillin resistant Staphylococcus aureus (MRSA) and 1 with E. coli; 1/10 patient had MRSA as the cause; 1/10 patient's microbiological cause could not be determined. Early images revealed increased zygomatic region pooling in 2/10 patients and increased temporal region flow and blood pool in 8/10 patients, respectively. Delayed images showed increased bone uptake in 10/10 patients. Localized abnormal tracer uptake was shown by SPECT/CT in the mastoid temporal (4), petrous (4), squamous temporal (1), sphenoid (2), zygomatic (3), basi-occiput (2), maxillary bone (2) and showed destructive changes in seven. Conclusion: Our study reveals that when combined with clinical characteristics, microbiological culture, structural imaging, and patient's immunocompromised status, TPBS with SPECT/CT exhibits great diagnostic performance as a means of diagnosing SBO.
| Case | Age/Sex | Presenting complaints; DM/HTN | Bone Scan Flow/pooling/delayed | Radiological Findings | Microbiological culture | |
|---|---|---|---|---|---|---|
| 1. Left skull base osteomyelitis - post mastoidectomy | 65/M | Fever, ear discharge, headache, reduced hearing; DM+/HTN- | Increased/increased/Increased tracer uptake(TU) in petrous temporal & basi-occiput | HRCT-Thinning of tegmen tympani; MRI-Left Otomasloiditis & osteomyelitis of left base of skull |
Pseudomonas aeruginosa | |
| 2. Left otitis externa -post mastoidectomy | 46/M | Fever, diplopia; DM+/HTN- | Increased/Increased/Increased TU in temporal bone (petrous, mastoid) & temporomandibular joint (TMJ). | CT&MRI- Aggressive otomastoiditis with left ICA thrombosis | Pseudomonas aeruginosa | ESR-38(0- 7mra/hr)- elevated |
| 3. Left malignant otitis externa s/p left cortical mastoidectomy | 77/M | Ear discharge, headache, facial palsy; DM+/HTN+ | Increased/increased/Increased TU in petrous temporal & Sphenoid bone. | HRCT- left CSOM with mastoiditis with ossicular erosions & mastoid bony destruction | Pseudomonas aeruginosa | |
| 4. Right malignant otitis externa | 40/M | Ear discharge, reduced hearing, diplopia; DM+/HTN- | Increased/increased/Increased TU in right mastoid temporal bone. | CT- S/0 malignant otitis externa, coalescent mastoiditis MRI- right mastoiditis with malignant otitis extema | Pseudomonas aeruginosa & E. | CRPH-7.3 (0-1 mg/1)- elevaied |
| 5. Right malignant otitis externa | 80/M | Ear discharge, ear pain, reduced hearing; DM+/HTN+ | Increased/increased/Increased TU in right mastoid and squamous part of temporal bone. | NA | Pseudomonas aeruginosa | |
| 6. Left skull base osteomyelitis - post mastoidectomy | 70/M | Ear discharge, ear fullness, facial palsy; DM+/HTN+ | Increased/increased/Increased TU in left mastoid bone. | CT- left middle ear cavity involvement with erosion of mastoid cortex; | Pseudomonas aeruginosa | |
| 7. Right recurrent otitis externa with osteomyelitis | 73/M | Fever, ear pain with an episode of seizure; DM+/HTN+ | Increased/increased/Increased TU involving right zygomatic and right TMJ. | HRCT- Right mastoiditis MRI-Peripherally enhancing collection in right prczygomatic region. |
MRSA& Pseudomonas aeruginosa | ESR- 62(0- 7mm/hr)- elevated |
| 8. Right skull bone osteomyelitis with chronic otitis | 74/M | Fever, ear discharge, reduced hearing, facial palsy; DM+/HTN+ | Increased/increased/IncrMsed TU in right petrous temporal bone, sphenoid body and basi-occiput region. | HRCT-lytic destructive lesion in petrous part of temporal bone and occipital bone; MRI- right oto- mastoidilis with diffuse skull base involvement | Pseudomonas aeruginosa | |
| 9. Left skull base osteomyelitis sinonasal mucormycosls- Invaslve | 46/F | Fever, Ear discharge, pain; DM+/HTN- | Increased/increased/Increased TU involving left zygomatic bone, frontal process of left maxilla bone, sphenoid bone. | NA | Sterile culture. | |
| 10. Right skull base osteomyelitis (?mucormycosis) | 57/F | Fever, Eye-lid edema, ear discharge, facial palsy; DM+/HTN+ | Increased/increased/Increased TU in right zygomatic, pterygoid, mastoid antrum, maxillary bone | MRI- invasive sinusitis in right maxillary, ethmoid and sphenoid with orbital involvement. | Pseudomonas aeruginosa | CRPH-121 (0-1 mg/l)- elevated |
Infection 5: When the source of infection is a puzzler: Consider 18F FDG PET/CT
Tanvi Sarwal, Deepanksha Datta, Sameer Taywade, Rajesh Kumar
Department of Nuclear Medicine, AIIMS, Jodhpur, Rajasthan, India
Introduction: In patients with fever of unknown origin (FUO), determination of the cause is challenging. 18F Fluorodeoxyglucose Positron Emission Tomography/ Computed Tomography (18F FDG PET/CT) is a commonly used modality for evaluating these patients when conventional modalities are inconclusive. In this study, we investigated the role of 18F FDG PET/CT in evaluating patients with FUO. Materials and Methods: This was a retrospective single-centre study conducted in the department of nuclear medicine, AIIMS Jodhpur. Our inclusion criteria were PET/CT scans done for patients with FUO, for which all the relevant investigations and follow-ups were available. The exclusion criteria were PET/CT done for other indications other than FUO. The PET/CT findings were compared with the final clinical outcomes. The gold standard for diagnosis was taken as histopathological and/or microbiological evidence of disease. All patients were followed up for outcome evaluation. Results: 30 PET/CT scans of 28 patients met the inclusion criteria. The mean age of the participants was 44.7 years (range: 2 to 70 years). The male:female ratio was 2:1. The true positives on PET/CT were 65% (19/28 patients). Out of these 19 patients, the final diagnosis was tuberculosis (3 patients), infective endocarditis (5 patients), pneumonia (2 patients), disseminated histoplasmosis (1 patient), pericarditis (1 patient), hemophagocytic lymphohistiocytosis (1 patient), prostatitis (1 patient), Hodgkin's lymphoma (1 patient), neuroendocrine tumour (1 patient), catheter-related bloodstream infection (1 patient), and neutrophilic dermatosis in 1 patient. The median SUVmax of the true positive patients was 6.7. The false positives on PET/CT were 6% (2/29 patients). Out of these two, one patient had diffuse uptake in the tongue muscles, and one patient had thickening along the AV groove of the heart, which turned out to be a hematoma. The false negatives were 3% (1/29 patients). This patient was finally diagnosed with Coagulase-negative Staphylococcus bacteremia. He was treated with systemic antibiotics and recovered. The true diagnosis was unknown after extensive investigations in 24% (7/29 patients). Out of these, 4 patients died undiagnosed despite extensive in-patient investigations, and 3 patients are still under evaluation. The erythrocyte sedimentation rate (ESR) was elevated in 23/28 patients (82.1%) and the C-reactive protein (CRP) was elevated in 100% of patients. Overall, the pooled sensitivity of PET/CT was 95%. Conclusion: This study demonstrates that PET/CT is a valuable diagnostic tool in evaluating patients with FUO. Physicians should consider routine PET/CT scans early in the course of disease for patients with FUO where diagnostic cues are absent. In the patients wherein CT-guided biopsy was inconclusive, PET-guided biopsy could be helpful in sampling from the metabolically active part of the lesion. Further multi-centre prospective studies should be done to validate these findings.
Infection 6: Effect of hemoglobin, total leukocyte count, ESR and blood glucose on 18F-FDG leukocyte labelling
Ajay Kumar, S. S. Prashar, A. Kumar, A. Bhattacharya, B. R. Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: Radiolabelled leukocytes are useful for the imaging of inflammation and infection. In the present study high specific activity 18F-FDG was used to label the leukocytes and to determine the factors affecting the labeling efficiency. Materials and Methods: The leukocyte labeling procedure was performed with high specific activity 18F-FDG in a sterile environment according the procedure described by Bhattacharya et al. The data was tabulated and analyzed using SPSS software, version 25. Results: The study consisted of 32 patients, 20:12;F:M, mean age was 43.98 ± 16.5 yrs (range 18-76 years). The radiolabelling procedure was carried out successfully, with mean labeling efficiency 83.98 ± 15.57 %. The mean hemoglobin, total leukocyte count, ESR and blood glucose was 11.2 ± 2.2 g/dL, 5.8 ± 3.4×103 L (neutrophils = 0.69), 37.93 ± 23.0 and 105.7 ± 31.6 mg/dL, respectively. The mean initial 18F-FDG added in the leukocytes suspension was 8.80 ± 1.05 mCi (range 6.6 – 12.10 mCi). The mean injected 18F-FDG labeled leukocyte activity was 4.7 ± 1.1 mCi (range 2.19-6.9 mCi). A strong negative correlation (corr- coefficient -0.94) was found between the blood glucose and labeling efficiency. Other parameters showed insignificant impact on the labeling efficiency. Conclusion: The in-house labeling of leukocytes with high specific activity 18F-FDG is safe procedure with a high labeling efficiency.
Infection 7: The advancing role of 18F-FDG labeled autologous leukocytes PET/CT scan in patients with cardiac interventions and infections
Ritanshu Solanki, Anish Bhattacharya, Yamini Mathur, Vikas Suri, Sarika Sharma Prashar, Ajay Kumar, Rajender Kumar, Prashant Panda, Bhagwant Rai Mittal
Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Introduction: Several radiotracers are currently used for infection imaging with both SPECT and PET. However, cardiac infections are difficult to detect on imaging. 18F-FDG PET/CT is a sensitive technique, however, variable physiological 18F-FDG uptake in the normal myocardium reduces its specificity and necessitates exhaustive patient preparation for the scan. 18F-FDG LAL PET/CT, combining high sensitivity and specificity of radio-labeled leukocytes with excellent resolution of PET/CT, is useful in abdominal and skeletal infection imaging. We aimed to study the diagnostic utility of 18F-FDG LAL PET/CT scan in patients with cardiac interventions and infections, in view of the limited available literature in this area. Materials and Methods: We reviewed our data from 2018-2023 for 18F-FDG LAL PET/CT scans performed on patients for pacemaker and pacemaker lead infections, suspected post-Bentall's procedure infection, rheumatic heart disease (RHD) post valve replacement, cardiac transplant with stent graft infection, infective endocarditis, vascular graft infection and abdominal aorta mycotic aneurysm infection. The demographic, clinical, biochemical, radiological investigations and blood culture data were evaluated to study the diagnostic efficiency of the scan. Blood culture was considered the gold standard; if it was negative, overall clinical, biochemical, and radiological investigations were used to assess concordance with the 18F-FDG LAL PET/CT scan. Results: Thirty patients (26 males, 4 females) with a mean age of 52.9 years, with pacemaker-related infection (n = 12), post-Bentall procedure (n = 4), RHD post valve replacement (n = 2), cardiac transplant with stent graft infection (n = 1), infective endocarditis (n = 9), aorto-femoral bypass with graft infection (n = 1) and abdominal aorta mycotic aneurysm (n = 1) were included in the study. TLC, ESR, CRP, and serum procalcitonin had median values of 12212/mm3 (IQR 7900-13400), 55.33 mm/hr (IQR 36-69), 66.70 mg/L (IQR 6.23-88.5) and 3.898 (IQR 0.11-12.42) respectively. Spearman correlation coefficient did not relate the lesion SUVmax with TLC (rho = 0.0548), ESR (rho = 0.190), CRP (rho = 0.191), and procalcitonin (rho = 0.0864) probably due to the small sample size. 18F-FDG LAL PET/CT was positive in 23/30 and negative in 7/30 patients; blood culture was positive in 23/30 and negative in 7/30 patients. 18F-FDG LAL PET/CT showed a sensitivity of 91.3% [95% CI- 71.96-98.93%] and specificity of 71.43% [95% CI- 29.04-96.33%] with 2/30 [6.67%] false negative (likely due to prolonged antibiotic course before the scan) and 2/30 [6.67%] false positive (likely due to unreliable blood culture done from different laboratory and difficulty in conclusively confirming infection by tissue culture in cardiac infections) results. 18F-FDG LAL PET/CT was concordant in 86.6 % of patients with overall diagnosis based on clinical, biochemical, and radiological features. Within the different sub-groups, the highest sensitivity [100%] and specificity [100%] were found in patients with infective endocarditis. Conclusion: The results of this initial study indicate that 18F-FDG LAL PET/CT is a reliable non-invasive imaging technique to accurately localize and direct medical or surgical intervention in patients with suspected cardiac infection. However, a more detailed study on a larger number of patients would be required to validate these results.
Infection 8: Standardization/optimization of peptide amount for efficient radiolabeling of 68-Ga-NOTA-UBI
Nishant Rana, N. Singh, P. Thakral, Jyotsna, D. Khichi, M. Koley, J. Gupta, S. S. Das, D. Malik, I. B. Sen
Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurugram, Haryana, India
Introduction: Ubiquicidin (UBI) 29–41 is a cationic, synthetic antimicrobial peptide fragment that binds specifically with the anionic microbial cell membrane at the site of infection. It can be chelated with a bifunctional chelating agent NOTA to allow complexation with 68-Ga. The labelling yield and labelling efficiency of the complex varies with the amount of peptide used for the radiosynthesis. In the current study we aimed at standardizing the optimum amount of NOTA-UBI peptide for 68-Ga-NOTA-UBI labelling to attain maximum labelling yield and labelling efficiency. Materials and Methods: NOTA-UBI peptide was procured from ABX, Germany. 68-Ga was obtained from a 1110 MBq 68-Ge-68-Ga generator (Isotope Technologies Graching – ITG). A total of 18 radiosynthesis were carried out and for each synthesis, 555 MBq (15 mCi) of 68-Ga-Cl3 was added to the 5M sodium acetate buffer followed by addition of NOTA-UBI peptide. A varying amount of peptide ranging from 30 µg to 80 µg (Peptide concentration: 1 µg/µL) was used for 3 synthesis each to obtain statistical significance. The reaction mixture was then heated at 90o C for 12 minutes and then filtered through activated C-18 SEK PAK cartridge. The trapped 68-Ga-NOTA-UBI complex was eluted using 70% ethanol. The radiochemical purity (RCP) of the labelled complex was evaluated using radio-TLC with iTLC-SG strips as stationary phase and 0.1 M sodium citrate as mobile solvent phase. Results: Time taken for the synthesis after elution was 28.4 ± 1.3 minutes. All the synthesized complexes were free from any particulate matter and were colorless in appearance. The maximum labelling yield (79.5 ± 0.55%) and labelling efficiency (95.46 ± 0.49%) was obtained using 70µg peptide, considering the physical decay of the radionuclide during the synthesis. Further increase in the amount of peptide to 80µg did not result in any significant increase in labeling yield (78.8 ± 0.30%) and labelling efficiency (94.8 ± 0.30%). Conclusion: From the present study we concluded that 70 µg of NOTA-UBI peptide is the optimum amount for obtaining maximum labelling yield and labelling efficiency for the synthesis of 68-Ga-NOTA-UBI.
Category: Neurosciences
Neuro 1: Role of PSMA PET-CT in detection of residual/recurrent malignant brain tumours
Mansha Vohra, Ram Singh Meena, Himanshu Bansal, Bhawani Shankar Sharma, Jitendre Singh Solanki, Anushree Punia, Shikha Dhal, Sumit Goyal
Department of Nuclear Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, India
Introduction: PET has emerged as an additional prominent non-invasive imaging modality for CNS tumours. For detection of recurrent /residual disease, the available modalities are MRI & FDG PET-CT. There are few limitations of these modalities in detection of residual/recurrent disease in brain parenchyma post-treatment. It is vital to investigate the concept of neovascularization of the tumour tissue with help of PSMA PET-CT in detection of residual/recurrent disease. It could not differentiate the grading of tumour but it is very helpful to differentiate viable and non-viable tumour tissue after the treatment. Materials and Methods: A prospective analysis of MRI/ histopathological proven patients of brain tumours with recurrent / residual lesions (n = 30; age range 08-70 years; mean age 51.4 years; Male to female ratio 5:1) was evaluated. All the patients were treated earlier, either in combination or solely with surgery, radiotherapy or chemotherapy. The patients were referred for PSMA PET-CT on the basis of clinical and imaging suspicion of residual / recurrent disease. MRI imaging follow up was considered as gold standard for recurrent/residual diagnosis which were acquired within 10 to 15 days after or before PSMA PET-CT. In 15 patients FDG PET-CT was also performed in order to compare the universal tracer with PSMA PET-CT. Results: Thirty patients who underwent PSMA PET-CT investigation for post-treatment monitoring were diagnosed as primary brain or spinal cord tumors. On region based disease analysis, 26 patients had cortical parenchymal lesions, whereas remaining 4 had a lesion in the brain stem. Out of 30 patients, PSMA PET-CT and MRI were concordant in 27 patients (90%) for presence and absence of disease. On clinical follow-up of 12 months of the patient who were negative for PSMA PET-CT but positive for MRI, there was no progressive deterioration in signs and symptoms and the follow-up MRI scans showed no significant interval change. In 15 patients, where comparative study of PSMA PET-CT and FDG PET-CT was conducted, PSMA PET-CT was more accurately positive than FDG PET-CT. This may be due to higher physiological uptake of FDG in brain and PSMA has near about no uptake. Conclusions: This study concluded that PSMA PET-CT has higher diagnostic accuracy as compared to conventional imaging for detection of suspected residual / recurrent disease in malignant brain lesion patients and also useful in searching the theragnostic applications.
Neuro 2: Adenosine-based nucleolipid-MPP conjugated liposomes loaded with 99m Tc: Targeted SPECT imaging of the brain for early disease diagnosis
Divya Gautam, Shubhra Chaturvedi, Raj Kumar Dutta, Presenjit, Ritika Chaudhary, Vishakha Chaudhary, Sunil Pal, Anil Kumar Mishra
Centre for Nanotechnology, Indian Institute of Technology, Roorkee, Uttarakhand, India
Introduction: Advancements in the field of nanomedicine have opened up new avenues for innovative approaches to disease diagnosis and imaging. This study provides a unique nanocarrier system consisting of Adenosine-lipid based liposomes covalently conjugated with Methoxy phenyl piperazine (MPP) and loaded with 99m Tc for Single Photon Emission Computed Tomography (SPECT) imaging applications. Materials and Methods: Adenosine-lipid conjugated with MPP was designed and synthesised using multistep organic synthesis. Starting with the synthesis of nucleolipids and then conjugation with MPP, the nucleolipids-based liposomes were synthesised using the thin-film hydration method. Briefly, the MPP-conjugated nucleolipid was dissolved in the DCM/Water mixture. Then, the solution was removed under reduced pressure to form a thin lipid film. Liposomes were then characterised using DLS, Zeta potential, SEM, etc., along with stability assessment. After that, the 99m Tc was encapsulated within the liposomes, and conditions like pH, time, and Concentration of the reducing agent were optimised for best radiolabelling efficiency. In vitro studies like haemolysis and MTT were also done for blood biocompatibility and cell cytotoxicity. Further, In vivo experiments and SPECT imaging will also be done to validate the synthesised liposomes. Results: Adenosine-lipid conjugated with MPP was successfully synthesised and characterised using different spectroscopic techniques like UV, NMR, IR and mass spectrometry. The Dynamic Light Scattering (DLS) analysis revealed that the synthesised liposomes had an average particle size of approximately 100nm, and zeta potential was measured at -29 mV, indicating good colloidal stability. The SEM images revealed the spherical morphology with a smooth bilayer structure. The radiolabelling with 99mTc achieved an efficiency of >90%, confirming the successful loading of the radiotracer. Cell viability assays and hemolysis assays demonstrated that formed liposomes exhibited no significant cytotoxic effects on the tested cell lines and showed blood biocompatibility. Conclusion: In conclusion, the findings of this study showed the versatility of nucleolipids-based liposomes for targeted diagnosis and imaging applications. By conjugating MPP with nucleolipid for precise targeting and 99mTc loading for high-resolution SPECT imaging, these liposomes may enhance diagnostic accuracy and advance the field of personalised medicine. By allowing early detection of diseases and facilitating customised therapeutic approaches, this study may have the potential to benefit patients and ultimately improve healthcare outcomes.
Neuro 3: Design and development of bifunctional molecular imaging probe targeting neurodegenerative disorders
Ritika Chaudhary, Shubhra Chaturvedi, Madhu Chopra, Divya, Presenjit, Vishakha Chaudhary, Ankur Kaul, Anil Kumar Mishra
Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India
Introduction: Neurological disorders pose a significant and increasing global health challenge, almost 50 million people are affected from neurodegenerative diseases worldwide. The 5-HT7 receptor (5-HT7R) is a subtype of the serotonin (5-hydroxytryptamine, or 5-HT) receptor family. Belonging to the class of G-protein coupled receptors (GPCRs) 5-HT7R can be a potential target for central nervous system (CNS) disorders, including schizophrenia and depression. The novelty of this work is the introduction of macrocyclic cage of DOTA and a triazine derivative. This Abstract present a comprehensive overview of the design and development of novel SPECT imaging probe targeting 5-HT7 receptor. Materials and Methods: The design and development of novel Bifunctional ligand was initiated and validated using computational studies. In silico studies were performed using following software; Autodock Vina, BIOVIA Discovery Studio Visualizer and GROMACS. The ligand showing best G-Score, binding affinity was selected for further development. The synthesis of novel radioligand was done using tryptamine and phenylpiperazine by reacting with 2,4,6-triamino-1,3,5-triazine. The resulting intermediate is further conjugated with macrocyclic cage of DOTA. Radiolabelling studies were carried out with 99mTc along with the optimization of radiolabelling parameters such as pH, the concentration of reducing agent and the incubation time. Cytocompatibility analysis was done on HEK cell line and hemocompatibility was analysed using human erythrocytes. Further, in vivo experiments and SPECT imaging will be done to validate the final molecule. Results: Computational investigations for the lead molecule was carried out and analysed with binding affinity -9.3 kcal/mol showing interaction with active site residues including Asp162, Val163, Phe343, Phe344, Trp340 and Ser347. The final ligand was synthesized with 87% yield. Further it was characterised using Mass spectroscopy and Nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR). Radiolabelling with 99mTc was found to be 92% confirmed the formation of radio-complex efficiently. The blood compatibility studies of final ligand showing less than 1.5% hemolysis of human erythrocytes suggesting insignificant RBCs destruction. Cytotoxicity assay on HEK cell line using MTT shows no significant toxicity at different time intervals. Conclusion: The results of this work demonstrated the successful synthesis of novel 5HT7 targeted ligand with a good efficiency for radiotracer showing this molecule will have potential to be used of brain SPECT imaging. The development of novel radioligand for the treatment of depression represents a promising way to learn more about this condition's neurobiology and offering new avenues for diagnosis and treatment.
Neuro 4: Development of 18F-AVT-011 for evaluating P-glycoprotein expression in cells to depict chemoresistance in glioma
Riptee Thakur, Manoj Kumar, M. V. Manjunatha, Harsha Sugur, Vani Santosh, Pradip Chaudhari, Pardeep Kumar
Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
Introduction: To study the uptake of 18F-AVT-011 in U87 (temozolomide sensitive) and LN18 cells (temozolomide resistant). To explore its role in predicting chemoresistance. Materials and Methods: 18F-AVT-011 was synthesized in our lab by a method published elsewhere1. The cell linesU87 (IC50 = 10-100μM) and LN18 (IC50 = 400-500 μM) were cultured in Dulbecco's modified eagle medium (DMEM). The MGMT levels and Pgp levels were evaluated by PCR and flow cytometry techniques respectively. The cells were detached using trypsin and then resuspended in equal proportion for the uptake study. Each test tube contained 1mL of cell suspension into which 10 μL (~ 0.74 MBq) of [18F]-AVT-011 was added and incubated for 15 min, 30 min, 60 min, and 120 min at 37ºC in a water bath. The blocking studies were performed by incubating the same cell suspension (1 mL) with 500-fold excess of Pgp blocking agent Tariquidar solution (5mM) for 30 min at 37ºC in a water bath and radioactivity was added as described above. The cell suspension was centrifuged. The pellet was washed thrice with normal saline, and the supernatant was collected separately in the other set of tubes. The radioactivity associated with cells and supernatant was counted in a gamma counter (Capnitec Inc), and the percentage of radioactivity bound to the cells was calculated. Results: 18F-AVT-011 was synthesized with radiochemical purity greater than 95%. methylation was more than 90% in U87 cells and ~ 4% in LN-18 cells. The Pgp levels were distinct in both cells. The Pgp levels were higher expressed in LN18 cells. The uptake of 18F-AVT-011 was 77.9 ± 0.5 % in U87 and 74.4 ± 2.9 % in LN18 cells at 15 min but it was 72.1 ± 1.7% in U87 and 9.6 ± 1.4% in LN18 and same was observed at 2 h. The radioactivity effluxed out of LN18 cells at a faster rate which may be due to the overexpression of Pgp. The blocking study showed an increase in the uptake of radioactivity after tariquidar blocking. Conclusion: 18F-AVT-011 maybe a potential radiotracer for imaging Pgp activity. The validation through animal study is in progress.
Neuro 5: Automated Synthesis of [11C]PiB via [11CH3OTf]-as methylating agent for PET imaging of β-Amyloid
Akhilesh Kumar Singh, Omkar Chauhan, Sanjay Gambhir, Manish Dixit
Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: A significant characteristic of Alzheimer's disease is the buildup of beta-amyloid, a byproduct of the APP, in the brain, which results in amyloid plaques. A cascade that results in brain cell death and cognitive deterioration is started by this buildup. As a result of the radiochemical production of 11C-labeled thioflavin derivatives, the Pittsburgh compound [11C]PiB, a PET radiotracer for detecting Aβ in Alzheimer's disease (AD), was developed in 2003. In addition to post-mortem autopsies for study, this invention enabled visualization of A plaques in the brains of living AD patients. By highlighting Aβ deposition, [11C]PiB allows early and accurate AD diagnosis across multiple stages, separating it from non-A dementias such as frontal temporal lobar degeneration (FTLD). This discovery has considerably increased clinical and scientific knowledge of AD. Materials and Methods: The chemicals and solvents used for the synthesis were purchased from Sigma Aldrich (India), Alfa Aesar (India), and LobaChemie (India) and used as such. For recording nuclear magnetic resonance (NMR) spectra, Bruker 400-800 MHz spectrometry was used. The precursor for [11C]PiB synthesis was prepared via a 7-8 step process, starting with anisidine and 4-nitrobenzoyl chloride. Yield was satisfactory. [11C]PiB radiosynthesis commenced with 11CO2 production via an 18MeV cyclotron (SHI, Japan). The 11CO2 was sequentially transformed into [11C]MeOH with LiAlH4, [11C]CH3I with HI, and swiftly reacted with activated methyl triflate to yield [11C]MeOTf for the final step. The generated [11C]MeOTf instantly reacted with the precursor, 2-(4-aminophenyl)benzo[d]thiazol-6-ol (6-OH-BTA-0), dissolved in of dry acetone and acetonitrile (1:1µl). The methylation of the precursor was performed for 4 min at 35 ℃. The crude [11C]PiB was purified with solid phase cartridges, tC18, and the trapped product was eluted with ethanol and diluted with saline to afford the desired product. The total duration for the synthesis of [11C]PiB took approximately 20 minutes. Results: The precursor was synthesized with a 50% yield and >97% chemical purity. Radiosynthesis of [11C]PiB achieved >98% radiochemical purity, demonstrating successful production. The specific activity of the final product was determined using standard procedures and found to be 110-121 mCi/μmol (with an average of 110 ± 11 mCi/μmol). Conclusion: We have successfully synthesized the precursor which was initiated with N-(chloromethyl)-4-(6-methoxybenzo[d]thiazol-2-yl)aniline from 4-methoxy aniline and 4-nitrobenzol chloride. The process yielded approximately 50% of the desired compound with a chemical purity of around 97%. The precursor, 2-(4-aminophenyl)benzo[d]thiazol-6-ol, was then used to synthesize [11C]-PiB using [11C]CH3OTf as a methylating agent. Purification was achieved through solid-phase cartridges, resulting in a decay-corrected radiochemical yield of 35-40% and a radiochemical purity exceeding 97%. This synthesis technique has been crucial in the study of Aβ imaging for Alzheimer's disease.
Neuro 6: Intercorrelated regional cerebral metabolism and the differential effect of electroconvulsive therapy
P. Santhosh Kumar, Rajesh Kumar, Sameer K. Taywade
Department of Nuclear Medicine, AIIMS, Jodhpur, Rajasthan, India
Introduction: Studying the regional cerebral glucose uptake pattern has further extended our understanding in many neurodegenerative and neuropsychiatric disorders. Electroconvulsive therapy (ECT) is the most effective treatment available for common psychiatric disorders like schizophrenia and major depressive disorder (MDD). However, the changes produced by ECT in the brain have not been completely elucidated. In this study we intend to present the changes produced by ECT in the glucose uptake of various regions of the cerebral cortex by studying their intercorrelation among each other. Materials and Methods: It was a prospective study that included 10 patients with drug refractory MDD who were prescribed ECT by their treating Psychiatrist and underwent FDG PET/CT brain within 72 hours before and between 7-14 days after the complete course of ECT. The software package used to perform image analyses was Cortex ID (GE Healthcare, Waukesha, WI, USA). The pre & post ECT images were normalized to cerebellum and regional FDG uptake patterns in the form Z-scores and their differences between the two studies were obtained. The Z-scores and their differences obtained for each region were intercorrelated with that of other regions and analyzed. Results: On normalization with cerebellum, on the pre-ECT FDG images, a moderate to strong positive intercorrelation of the regional Z-scores was observed among all the regions of the cerebral cortex. Post ECT images obtained at full clinical remission also showed similar positive intercorrelation among the Z-scores of the cerebral cortical regions. In the differences of Z-scores obtained for each cortical region, positive intercorrelation was observed among all the regions except for the mesial temporal region which showed a negative intercorrelation of differences with rest of the regions of the cerebral cortex. Conclusion: Prefrontal hypometabolism is a described finding for MDD. Existence of positive intercorrelation among all the cortical regions in the pre-ECT FDG images, suggest the interdependency of regional cerebral glucose uptake with one another. Patients with lesser glucose uptake in one of the cortical regions is therefore expected to have lesser glucose uptake in other regions than patients with better uptake. Although ECT has produced changes in the cerebral glucose uptake, the positive intercorrelation continuing on post-ECT images signify the persistent interdependency of regional uptake. However, ECT has a differential effect in different cortical regions. This differential effect is brought to light by studying the Z-score differences between the pre & post ECT images. ECT is known to accentuate the prefrontal hypometabolism of MDD, the positive intercorrelation of differences with other regions, signify accentuation in other regions too. However, the mesial temporal regions’ negative intercorrelation signifies the opposite effect of ECT, where the hypometabolism is attenuated. Worsening of hypometabolism doesn't explain the clinical improvement in the patients after ECT. While, improvement of the mesial temporal metabolism should be the probable explanation for the clinical effect of ECT.
Neuro 7: Analysis of various metabolic patterns in brain on F18 FDG PET-CT patients with autoimmune encephalitis
Siddharth Sahu, Deepanksha Datta, Rajesh Kumar, Sameer Taywade
Department of Nuclear Medicine, AIIMS, Jodhpur, Rajasthan, India
Introduction: Autoimmune encephalitis(AE) is antibody mediated disorder which has varied spectrum of clinical features. It may be associated with antibodies against neuronal cell-surface or synaptic proteins. FDG PET-CT of brain can contribute in solving the diagnostic dilemma of autoimmune encephalitis. Materials and Methods: A retrospective descriptive study was performed in department of nuclear medicine, AIIMS Jodhpur in patients fulfilling graus criteria of autoimmune encephalitis who underwent FDG PET-CT brain and autoimmune panel. Patterns of FDG uptake were analysed visually and by cortex ID software. Results: 14 patients met inclusion criteria of which 5 (36%) were antibody positive. 4 out of 5(80%) had anti NMDA antibody, of which 3(60%) showed hypometabolism in bilateral parietotemporal occipital lobe with either preserved or increased metabolism in basal ganglia and other subcortical structures & 1(~20%) showed hypometabolism in left hemi-cerebrum, left half of basal ganglia-thalamus and right cerebellum with hypermetabolism in left hippocampus, mid brain and right half of basal ganglia-thalamus. 1/5 (20%) patient had anti LGI-1 antibody and demonstrated hypometabolism in bilateral temporal, parietal and occipital cortices with hypermetabolism in basal ganglia and posterior cingulate cortex. 9/14(64%) did not show antibodies on autoimmune panel and had variable metabolic patterns in brain.3/9(33%) showed features of limbic encephalitis in the form of diffuse hypermetabolism in bilateral basal ganglia, thalamus, mesial temporal lobe and bilateral parafalcine region. 2/9(22%) showed patchy pattern of hypometabolism in various cortical region, and 4/9(45%) showed diffuse hypermetabolism in basal ganglia with diffuse hypometabolism in cerebral cortex various parts. Conclusion: FDG PET- CT can be helpful tool in early diagnosis of AE especially when other modalities are inconclusive and structural changes are not yet evident on MRI. Various metabolic patterns in brain can be observed in both antibody positive and negative clinically suspected patients of AE. However hypermetabolism in basal ganglia is the most common finding seen in such patients.
Neuro 8: 18F-DOPA PET in Parkinson disease-correlation with clinical findings and review of drug history
Darshan Thakrani, Shwetal Pawar, Niraj Jain1, Sangeeta Ravat1
Departments of Nuclear Medicine and 1Neurology, Seth G.S. Medical College and KEM Hospital, Mumbai, Maharashtra, India
Introduction: Parkinson disease (PD) is the second most common cause of neurodegenerative disease, after Alzheimer's dementia. The clinical diagnosis alone may not accurate enough especially in the early stages of the disease and this reinforces the importance of the functional imaging aiming pathophysiology of disease process. 18 F-DOPA is a positron emission tomography (PET) agent that measures the uptake of dopamine precursors for assessment of presynaptic dopaminergic integrity and has been shown to accurately reflect the monoaminergic disturbance in PD. [18F]-DOPA uptake is decreased in putamen in virtually all patients with PD, even in the early stage of disease. Small clinical trials have demonstrated high sensitivity and specificity for 18F-DOPA PET in PD, but little data exist about 18F-DOPA PET's role in differentiating IPD from other causes. The aim of the study is to determine diagnostic accuracy of 18F DOPA PET in differentiating IDP from other close differential diagnosis having parkinsonian features. Methods: In this retrospective study of 70 patients (48/22-M/F), who were injected with mean dose 5 mCi(185MBq) of 18F-DOPA. The scan was interpreted by visual (qualitative) analysis of 18F-DOPA uptake in basal ganglia nuclei caudate and putamen. The reduced 18F-DOPA uptake was classified into mild, moderate, severe and normal by extent of involvement of bilateral caudate and putamen. Patients with only typical features of PD as tremors, bradykinesia, rigidity and imbalance were classified into suspected and clinically diagnosed (on levodopa and carbidopa) cases of IPD, while patients showing typical parkinsonian symptoms with neurodegenerative features and speech difficulties were classified into suspected atypical PD. Patients having parkinsonian features with previous history of anti-psychotic and anti-epileptic drugs were classified into suspected drug induced (DIP). Results: 54/70 showed reduced F-18 DOPA uptake based on qualitative assessment. Amongst 25(36%) suspected PD, 19/25(76%) were positive and 6(24%) were normal (p <0.05). From 20(29%) patients of diagnosed PD 3/9/8 was mild moderate and severe PD respectively. 6 /17 patients suspected of atypical PD were normal, 4 were moderate, 3 were severe and 4 were normal. 6/8 (75%) of suspected DIP was normal and 2 were positive. Out of 25(36%) patients having symptoms of tremors, 19(76%) showed severe (p < 0.05), 6 showed moderate and 5 scan showed mild disease. From 27(29%) patients of bradykinesia and slowness of ADL, 14(51%) showed severe (p < 0.05), 8 showed moderate and 5 showed mild disease. From 14 patients with rigidity, 5/4/5 showed severe, moderate and mild disease respectively. Out of 8(11%) patients with speech difficulties, 5(62%) showed severe disease (p < 0.05). From 36 patients with unilateral symptoms, 8 patients showed contralateral involvement and 22 patients showed bilateral reduced dopamine update. Conclusion: 18F-DOPA-PET can differentiate IPD from other close clinical differentials having parkinsonian features, but we found more accurate in differentiating drug induced Parkinson disease. 18-F DOPA can be useful in early diagnosis of bilateral basal ganglia pathology with clinically unilateral symptoms. We could not differentiate between atypical and typical PD which was based on clinical features.
Neuro 9: Unmatched diagnostic potential of Cisternography (SPECT/CT), in detection of Normal Pressure Hydrocephalus
Ramya Subramani, R Subramani1, S Sanisetty1, P Palanivel1, R K Arora2, M L Narayan1*
Department of Nuclear Medicine, All India Institute of Medical Sciences, Rishikesh, UK
Introduction: Normal pressure hydrocephalus (NPH) is a communicating hydrocephalus syndrome characterized by the presence of gait disturbance, urinary urge incontinence and cognitive decline. A variety of imaging modalities are available to evaluate NPH. CT and MR imaging are usually the first steps but the findings from these modalities are nonspecific. Radionuclide cisternography (RCG) is a functional imaging tool with documented use since 1950s. Hybrid imaging with SPECT/CT has led to major improvements in diagnostic accuracy by fusing functional studies with anatomic images. RCG is usually considered as a valuable alternative to MR imaging for patients who have contraindications to MR. Authors here present a suspected case of NPH, where RCG helped in resolving diagnostic dilemma, that persisted despite thorough clinical evaluation, conventional imaging and confirmatory CSF tap test or lumbar drainage. Case Report: A 60 years old female with progressively worsening gait disturbance, forgetfulness and urinary incontinence for the last 6 years was admitted and evaluated for Normal Pressure Hydrocephalus because of the high clinical suspicion. In spite of tapping of about 200-600ml in 3 consecutive days, there was no significant improvement in her symptoms. Hence, she was referred to the Department of Nuclear Medicine for Radionuclide Cisternography scan. The scan was performed following instillation of 99m-Tc DTPA(1mCi) in the sub-arachnoid space under aseptic precautions through the LP drain, under supervision of treating Neurosurgery team. Sequential static anterior-posterior and lateral images were acquired at 1,4,7 and 24hours post instillation (with Clamped LP drain throughout the study). SPECT/CT images were acquired at 4hours.
Discussion: Planar images reveal good instillation and ascent of tracer from the LP drain with significant reflux of tracer into bilateral ventricular system. Delayed migration of tracer over cerebral convexities noted at 7hours and persistence till 24hours. There was no evidence of abnormal tracer extravasation and leak noted throughout the study. Reconstructed coronal, sagittal and axial views demonstrated reflux into lateral ventricles in heart, comma and butterfly configurations respectively within 1hour of imaging. Additionally, localization of tracer was noted along the Sylvian fissures. Correlative CT images reveal significant dilatation of lateral ventricles with marked prominence of sulci and gyri, suggestive of diffuse cerebral atrophy. Considering all the scan findings diagnosis of NPH was established through scintigraphy. Conclusion: Radionuclide cisternography with SPECT/CT combines both functional and anatomic imaging, providing precise tracer localization and CSF dynamics. This case highlights the role of RCG even in setting of negative CSF tap test and indeterminate MR Imaging, thus effectively resolved the diagnostic dilemma and provided guidance for the precise management of the NPH.


Neuro 10: 18F-FDG PET/CT findings in patients with MRI proven mesial temporal lobe sclerosis
Malay Mishra, Deepanksha Datta, Sameer Taywade, Rajesh Kumar
Department of Nuclear Medicine, AIIMS, Jodhpur, Rajasthan, India
Introduction: Epilepsy is a common medical condition with a worldwide prevalence of 50 million. The most common subtype of medically refractory focal epilepsy is temporal lobe epilepsy. Mesial temporal lobe epilepsy (MTLE) is the most common subtype (constituting 50%) of temporal lobe epilepsy. 18F FDG PET/CT Brain is a highly sensitive modality in localizing the epileptogenic region, in combination with MRI and EEG findings. In our study, we aimed to relate PET/CT scan features with MRI findings in patients with MTLS. Materials and Methods: This was a retrospective study of patients who underwent epilepsy evaluation and were referred to department of nuclear medicine for PET/CT between January 2021 and August 2023. 124 epilepsy patients who underwent PET/CT were evaluated, out of which 23 patients whose MRI was suggestive of mesial temporal lobe sclerosis were included in the study. Patients who were seizure-free for at least 24 hours prior to the scan underwent PET/CT. There were no seizure episodes during the uptake period. Areas of brain hypometabolism were noted in PET/CT and compared with MRI findings of MTLS. Additional features in both the imaging modalities were also noted. MRI was taken as the gold standard. Results: Our study comprised of 23 patients, with a mean age of 27 years (range 11 to 58 years). There were 12 males and 11 females in the study. A total of 36 lesions in 23 patients were identified. In all 23 patients (100%), FDG PET/CT demonstrated hypometabolism in the mesial temporal lobe. In 6/23 (26.08%) patients, there were additional lesions on MRI, other than MTLS like antterior temporal dysplasia, in 5/6 (22%) patients. One patient had encephalomalacia with surrounding gliotic changes in the lingual gyrus on MRI. Of these 6 patienst, PET/CT did not show additional findings in 3 patients, however in other 3 patinest it showed hypometabsolim in 3 of them showed hypometabolism in the temporal lobe on PET, whereas 3 did not. Further, in 10 patients (43%), hypometabolism was observed on PET/CT in various areas of the brain, whereas MRI did not reveal any findings in the corresponding regions. Thus, out of 36 lesions, 23 (64%) were concordant on MRI and PET/CT and 13 (36%) were discordant. Out of these 13 findings, 10 additional findings were observed on PET/CT and 3 additional findings were noted on MRI. Conclusion: In all 23 patients diagnosed with MTLS on MRI, PET showed concordant findings of hypometabolism in mesial temporal lobe. Additionally, in 10/23 (43%) patients, areas of hypometabolism on PET were noted without corresponding MRI changes. Since surgery is the management of choice in these patients with medically refractory epilepsy, knowledge of additional PET findings is essential as it may affect post-surgical outcomes. Further multi-centric prospective studies are needed in this direction.



Neuro 11: Radiosynthesis of carbon-11-PBR-28 for TSPO-PET-MRI
Aishwarya Kumar, Atchayaram Nalini, Jitender Saini, Ravi Yadav, Monojit Debnath, K. Vijayalakshmi, T. N. Sathyaprabha, Chandana Nagaraj, Pardeep Kumar
Department of Neuroimaging and Interventional Radiology, NIMHANS, Bengaluru, Karnataka, India
Introduction: Translocator protein 18 kDa (TSPO), expression is up regulated in several human pathologies with inflammation, including many neuropsychiatric disorders that are known or suspected to have inflammation. Thus, PET imaging of TSPO is investigating as a biomarker to detect neuropsychiatric disorders at an early stage. Objective: To synthesize carbon-11 (11C) labeled PBR-28 in the chemistry module (GE Tracerlab FX2C). Materials and Methods: [11C] was produced as [11C]CO2 via [14N(p,α)11C] nuclear reaction using GE PETtrace cyclotron and passed on to the FX2C Tracerlab module. In module, [11C]CO2 was reacted with hydrogen gas at 350°C in presence of nickel catalyst and produced [11C]-CH4. [11C]-CH4 was trapped on Carboxen (60-80 mesh) whereas unreacted [11C]CO2 and H2O vapors were trapped on ascarite and sicapent trap respectively. [11C]-CH4 was released and undergo iodination at 740ºC to form [11C]-CH3I which recirculated in the loop and trapped on porapak trap at room temperature until reached to maximum activity. Once the maximum activity and time achieved, the temperature of the [11C]-CH3I trap comes down to 200ºC and released [11C]-CH3I through V17 and V18 introduced into the reactor and bubbled into the solution of desmethyl-PBR-28 [200 mg in 300 μL of 1/1/2 (0.5 N sodium hydroxide/ethanol/water)] for 2 min. Then the rection mixture was passed to the integrated preparative HPLC in the module [Figure 1]. The 11C-PBR-28 was purified using preparative HPLC. The labelling was checked by high performance liquid chromatography (HPLC). The labelling was more than 85% and further need to be purified through preparative HPLC. Results: The reaction mixture passed through preparative HPLC showed two different peaks [Figure 2], both were collected and to subjected to the quantitative HPLC. The standard reference of PBR-28 was also run, and its retention time was taken as reference to identify the peak for 11C-PBR-28. The reference standard peak was around 3.5 min [Figure 3a] and 11C-PBR-28 was observed at 3.7 minutes [Figure 3b]. Conclusion: The reaction mixture passed through preparative HPLC showed two different peaks [Figure 2], both were collected and to subjected to the quantitative HPLC. The standard reference of PBR-28 was also run, and its retention time was taken as reference to identify the peak for 11C-PBR-28. The reference standard peak was around 3.5 min [Figure 3a] and 11C-PBR-28 was observed at 3.7 minutes [Figure 3b].
Acknowledgements: We acknowledged ICMR for the funding.
Category: Oncology and PET
Onco 1: Lung biopsy -PET CT guided robot assisted procedures – An institutional experience
Anurag Jain, Abhishek Mahato, Awadesh Tiwari
Department of Nuclear Medicine, Command Hospital, Lucknow, Uttar Pradesh, India
Introduction: Lung biopsies are categorized based on access method and the purpose of the biopsy itself. The Tru-Cut biopsy technique offers a straightforward, safe, swift, and dependable approach for diagnosing lung mass lesions, especially when coupled with Robot assisted positron emission tomography computed tomography (CT) scans technique. The introduction of positron emission tomography-computed tomography (PET-CT) scans has significantly improved the staging and localization of cancer lesions. Combining this advanced imaging technology with robotic-assisted biopsy systems is a game-changer in the field. This method is a new cutting edge technique to identify various types of lung tumors and explore its efficacy in diagnosis. This study seeks to evaluate the diagnostic utility of the Tru-Cut biopsy in lung tumors with Robot assisted positron emission tomography computed tomography (CT) scans guided technique. Materials and Methods: A prospective examination encompassed 25 patients who underwent Robot assisted positron emission tomography computed tomography CT-guided Tru-Cut biopsies between Feb 2023 and Aug 2023. These patients were referred to our department with a diagnosis of lung mass lesions suspected to be neoplastic based on chest radiography and/or CT scans. The biopsy procedures were conducted using a 64- Slice GE Discovery 690 With Time of Flight (TOF) for conducting 18F FDG PET CT scans and Robot assisted PET CT guided ROBIO machine for PET CT image guided biopsy procedures. Biopsies were performed utilizing an 18 G and 17G semiautomatic needle with the coaxial technique and Robot assisted guidance of mapping the image guided track, Planned with target depth and orbital angle depending on the location lesion. Patient position were supine in 18 patients, lateral in 02 patients and prone in 05 patients. The procedure begins with the acquisition of high-resolution PET-CT images, which helps identify suspicious lesions and enables proper staging. The imaging data is then integrated with the robotic system, providing real-time feedback and navigation during the biopsy procedure. This synergy allows for targeted biopsy sampling, reducing the likelihood of missing significant lesions and minimizing the number of biopsy cores needed. Results: The study encompassed prospective 25 Robot assisted PET CT guided biopsy procedures and corresponding histopathology reports. Patient ages ranged from 20 to 75 years, with the highest incidence observed in the sixth and seventh decades of life. Of the cases, 03 (12%) were identified as benign lesions, while 22 (88%) were microscopically confirmed as malignant lesions. The predominant tumors were squamous cell carcinoma (35%), followed by adenocarcinoma (24%) and small cell lung carcinoma (21%). Additionally, non-specific inflammation was noted in 8% of cases. Conclusion: Robot assisted positron emission tomography computed tomography CT-guided Tru-Cut biopsy emerges as a straightforward, secure, and dependable procedure, boasting substantial diagnostic accuracy for identifying and subtyping lung cancer. The definitive determination of malignancy stands as a critical factor in making well-informed decisions regarding patient treatment. This determination hinges on meticulous clinical correlation with the patient's performance status, radiological findings, and comprehensive serological investigations. The Robot-Assisted PET-CT Guided Biopsy integrates the capabilities of robotic platforms and PET-CT imaging to enhance the precision and accuracy. Robot-Assisted PET-CT Guided Biopsies represent a significant advancement in the field of prostate cancer diagnosis. This innovative approach offers improved accuracy, reduced complications, and enhanced cancer detection rates.
Onco 2: Optimisation of patient workflow for PET-CT guided robotic biopsies – Experience at a tertiary care center – A technologist perspective
Awadhesh Tiwari, Anurag Jain, Abhishek Mahato
Department of Nuclear Medicine, Command Hospital, Lucknow, Uttar Pradesh, India
Background: The optimization of patient workflow in PET-CT guided robotic biopsy procedures is a critical aspect of improving the efficiency and efficacy of Nuclear Medicine. PET-CT-guided robotic biopsies have emerged as a precise and minimally invasive technique for obtaining tissue samples for diagnostic purposes. However, the success of these procedures depends not only on the accuracy of robotic systems but also on the seamless coordination of various components within the workflow. Also in a Nuclear Medicine department time is of essence due to decay of the radiopharmaceuticals and exposure of the healthcare staff performing the procedure. To optimize patient workflow, several crucial elements are addressed which can be categorised under three heads. Pre-procedure Planning: Thorough pre-procedure planning involves precise indication for the biopsy, lesion localization, selection of the appropriate robotic system, and patient-specific considerations. Patient Preparation:** Patient education and preparation are essential to alleviate anxiety and ensure cooperation. Clear communication regarding fasting requirements, medication instructions, and expectations for the procedure reduces potential delays. Equipment and Staff Preparedness:** Ensuring the availability and functionality of all necessary equipment, including the CT scanner, robotic system, and biopsy tools, is crucial. Additionally, a well-trained and coordinated healthcare team is vital to execute the procedure seamlessly. Efficient Procedure Workflow Sequencing from streamlining the sequence of steps, from initial imaging to robotic intervention and biopsy sample collection, minimizes patient exposure to radiation and reduces procedure time. Also exposure to healthcare staff is minimised. Post-procedure Management: Immediate post-procedure care includes monitoring for complications, pain management, and appropriate patient discharge. Clear post-biopsy instructions and follow-up appointments ensure a smooth transition from the procedure suite to recovery. Last and not the least is Data Integration and Analysis which involves collection and analysis of procedural data, including navigation trajectories and patient outcomes, facilitate continuous improvement in workflow optimization. Materials and Methods: This study was conducted in collaboration with Department of Medical and Surgical Oncology between April 2023- Jul 2023. A total of 55 patients underwent PET-CT guided robotic biopsies. PET-CT guided biopsies were performed on Perfint Robio system by team of two Nuclear Medicine physicians and two technologists. Patient workflow optimisation was evaluated under three heads 1) Appointment to procedure time 2) Procedure time 3) Post procedure time. Results: A total of 55 patients (37 Female and 18 Male) underwent the procedure. The mean age of the cohort was 55.54 years. Youngest patient was 16 years of age and Oldest patient was 74 year old. Minimum target depth was 10mm and maximum depth of targetted lesion was 125mm with an average depth of 53.8mm. Organ wise 04 prostate biopsies, 03 from axilla, 06 in breast, 26 in chest (lung + pleural lesion + mediastinal lymph nodes), 06 in peritoneal deposits, 08 in pelvic lesions and 02 bone biopsies. Patients symptom status and admitted patients has decreased pre-procedure time. Prone position for biopsy, lesion size, lesion depth and biopsy site were the most important factors affecting the procedure time. Female patients required relatively more time to ensure adequate privacy during the procedure. Conclusion: Optimizing patient workflow in CT-guided robotic biopsy procedures contributes to reduced patient discomfort, shorter procedure times, and enhanced diagnostic accuracy. This not only benefits patients by improving their overall experience but also benefits healthcare providers by increasing the efficiency of interventional radiology services. Continuous refinement of workflow processes, coupled with advances in technology and training, will further improve the precision and accessibility of CT-guided robotic biopsies in the future.
Onco 3: PET-CT guided robotic biopsies – An institutional experience
Abhishek Mahato, Anurag Jain, Richa Joshi, Vadlamani Suryaprakash, Rajesh Nair, Awadhesh Tiwari
Department of Nuclear Medicine, Command Hospital, Lucknow, Uttar Pradesh, India
Introduction: Traditionally, USG and CT-guided biopsies have been the primary methods for obtaining tissue samples. CT-guided biopsies are generally considered reliable, with reported accuracy rates ranging from 80% to over 98%. However, their success depends on various factors, including lesion location, type, operator expertise, sampling technique, and patient-related factors. Challenges arise when lesions are near critical structures or in complex anatomical regions. Different lesion types, such as solid masses and cystic structures, present varying levels of biopsy difficulty. Operator skill and experience significantly affect precision, as does the chosen sampling technique. Patient-related factors, such as body habitus, breathing patterns, and anatomical considerations, also impact procedural success and accuracy. Failed biopsies can result from various factors, preventing the acquisition of precise tissue samples. Sampling errors, where the biopsy may not fully represent the lesion or may miss the target entirely, can lead to incorrect diagnoses. Inadequate tissue samples, whether too small or fragmented, hinder accurate pathological assessment. Biopsy technique, including angles and pressure, influences sample quality, and tissue characteristics like location, texture, and consistency can be challenging. Operator expertise is crucial, as inexperienced practitioners may make errors during sample collection. Patient-specific factors like obesity or anatomical variations can complicate access to the target tissue. Complications such as bleeding, hematoma, or infections at the biopsy site can compromise sample quality. Tumor heterogeneity, where cells within a tumor vary, can yield inaccurate results if the sampled area lacks abnormal cell representation. Proper fixation and processing are vital for accurate diagnosis, as errors can degrade tissue and impede analysis. Technical limitations, especially for delicate or small tissues, make accurate biopsy challenging. Patient cooperation and positioning are essential to prevent errors caused by movement. Instrumentation issues, like malfunctioning tools, can lead to unsuccessful biopsies. Furthermore, previous treatments like radiation therapy or chemotherapy can modify tissue appearance, complicating accurate diagnoses. To mitigate the risk of failed biopsies and ensure reliable diagnostic outcomes, meticulous planning, skilled operators, and consideration of patient-specific variables are essential. This study was conducted to evaluate the benefits and limitations of PET-CT guided robotic biopsies at a tertiary care center. Materials and Methods: This study was conducted in collaboration with Department of Medical and Surgical Oncology between April 2023- Jul 2023. A total of 55 patients with previously failed biopsies underwent PET-CT guided robotic biopsies. PET-CT guided biopsies were performed on Perfint Robio system by team of two Nuclear Medicine physicians and two technologists. The note was made of the procedure time, number of needle passes, check PET-CT scans. While the robotic parameters incorporated were the orbital angle and target depth. Results: A total of 55 patients (37 Female and 18 Male) with previous failed biopsies underwent the procedure. The mean age of the cohort was 55.54 years. Youngest patient was 16 years of age and Oldest patient was 74 year old. Minimum target depth was 10mm and maximum depth of targetted lesion was 125mm with an average depth of 53.8mm. The suggested needle length by the machine is 30 mm longer than the target depth, with minimum being 40mm and 155mm with an average depth of 83.8mm. Minimum orbital angle used was 39.03 degrees and maximum orbital angle used was 67.08 degrees. Minimum craniocaudal angle was 3.68 degrees and maximum angle of 6.12 degrees. Organ wise 04 prostate biopsies, 03 from axilla, 06 in breast, 26 in chest (lung + pleural lesion + mediastinal lymph nodes), 06 in peritoneal deposits, 08 in pelvic lesions and 02 bone biopsies. 40 patients had oncolgical pathology while 05 patients had infective etiology - tuberculosis. 10 Biopsies were non representative or had no evidence of malignancy. Conclusion: Robotic guided PET-CT biopsies are user friendly and aid medical professionals in adapting to its application, thereby reducing the learning curve. It offers navigation of needle through complex trajectories with reliable accuracy decreasing the procedure time and number of needle pass and check CT. By minimizing operator fatigue it enables consistent and reproducible results, Moreover it streamlines the biopsy process, potentially reducing patient discomfort and recovery time. While robotic-guided biopsies offer numerous advantages, they also come with their own set of considerations, including equipment costs, training requirements, and the need for experienced operators. The decision to use robotic technology should be made based on a thorough evaluation of the specific clinical scenario and available resources.
Onco 4: Automated cassette-based synthesis of 68Ga-trivehexin and its quality control for routine production in a GMP environment
Jay Prakash Kumar, M. V. Manikandan, Ritwik Sinha, Ravi Chauhan, Manoj R. Chauhan, Uddeshya Narayan Jha, Varun Shukla, Santosh Gupta
Department of Nuclear Medicine, Mahamana Pandit Madan Mohan Malviya Cancer Centre, Varanasi, Uttar Pradesh, India
Introduction: 68Ga-Trivehexin is a PET radiopharmaceutical for imaging of αvβ6-integrin expression in head & neck and pancreatic cancer. Our aim was to label trivehexin with 68Ga with in automated synthesizer module. Materials and Methods: The production of trivehxin peptide labelled with 68Ga gallium is done with the use of the ITG Germany approved 68Ge-68Ga generator. Radiosynthesis parameters were setup by specific labelling conditions(95ºC) with the automated synthesizer IQS-TS module. The reagent kit, disposable cassettes were used in the process, were purchased from ITM, Germany. The parameters such as temperature, precursor concentration, 0.22 μm filter integrity, reaction time and product purification setup (C-18 cartridge) are set up in control program. The 68Gacl3 was eluted in the reactor with a mixture of trivehexin peptide with sodium acetate buffer. The reaction vial was heated at 95ºC for 5-7 minutes for labelling. After heating product is purified on C-18 cartridge. The overall synthesis time was 15-17 minutes. Radiochemical purity of final product was quantitively analysed by instant thin layer chromatography on TLC Scanner. Results: The average radiochemical purity of the product was >95% with RF at 0.068 (n = 4) with the total amount of the peptide in the preparation of 50µg. Conclusion: The fully automatic and simplified synthesis of 68Ga trivehexin was obtained on cassette-based module with high radiochemical purity. Ready to use consumables are available to help streamline routine clinical production in a GMP environment.
Onco 5: Evaluating the role of 18F FDG PET/CT in postoperative management of renal cell carcinoma
P. Bose Thakur, S. Deswal, L. Kakkar, M. Pradhan, M. M. Singh
Department of Nuclear Medicine, Dr. Ram Manohar Institute of Medical Sciences, Lucknow, India
Introduction: Renal cell carcinoma (RCC) is a prevalent kidney tumor, with surgery being the primary treatment for stage I to III and in some stage IV patients. However, the postoperative phase necessitates crucial decisions for surveillance, disease monitoring and therapies. This study investigates the value of postoperative PET/CT in patients with histopathologically (HPE) confirmed RCC. Materials and Methods: This retrospective study examined 16 patients who had undergone radical nephrectomy for RCC and subsequent 18F FDG PET/CT scans at the Department of Nuclear Medicine from January 2019 to July 2023. Clinical, HPE, and PET/CT data were analyzed, with patient treatment courses and performance status tracked during follow-up. Results: Among the 16 patients, 10 (62.5%) had positive PET/CT scans, while 6 (37.5%) had negative scans. 12 patients had Clear cell carcinoma, whereas 2 patients had Papillary type I and 2 patients had Papillary type II tumors. All three stage pT1 patients had negative PET/CT results. 3 patients had tumors with pT2 stage, out of which one patient with pT2b stage (also having abundant desmoplastic stroma on HPE) had a positive PET/CT. 5 out of 6 (83.33%) pT3 patients and all pT4 patients had positive PET/CT scans, indicating a significant association (p = 0.034, using Fisher's exact test) between pathological stage and PET/CT positivity. Moreover, a strong correlation (r = 0.82) was observed between the percentage of tumor necrosis on HPE and distant metastases detected on PET/CT. Moderate (r = 0.37)and weak(r = 0.239) correlations existed between tumor size and ISUP grading respectively and PET results, indicating that factors other than these such as renal sinus invasion and extension beyond Gerota's fascia also plays an important role in probability of having a positive restaging PET/CT. Patients with a positive PET/CT scan were often asymptomatic (except one patient) for locoregional or distant metastases, demonstrating PET/CT's ability to identify clinically occult metastases. Importantly, in 70% of PET/CT-positive cases, the treatment approach shifted from surveillance to systemic therapy, even though these patients had been preoperatively evaluated following NCCN ver 3.2022 practice guidelines. Patients who were diagnosed with distant metastases on PET/CT had a poorer ECOG performance status on follow up. Conclusion: This study underscores PET/CT's essential role in post-nephrectomy RCC management. It highlights the correlation between pathological T stage and PET/CT outcomes, particularly for stage >T2b tumors, which often necessitate post-nephrectomy systemic therapy and/or metastasectomy. Additionally, the percentage of tumor necrosis emerged as an independent predictor of PET/CT results, emphasizing its clinical relevance. PET/CT's capacity to detect clinically occult metastases and guide treatment decisions holds promise for enhancing patient outcomes through early detection and tailored post operative management. Nevertheless, given the limited number of participants in this study, there is a clear imperative for larger-scale research to validate and substantiate these findings effectively.
Onco 6: Novel fluorinated osimertinib analog for medical nuclear imaging of EGFRm-positive non-small cell lung cancer
Y. Brief, H. Grievink, G. Abourbeh, E. Mishani, O. Shamni
Department of Nuclear Medicine, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
Introduction: Non-small cell lung cancer (NSCLC) comprises the majority of lung cancer cases. Activating mutations in NSCLC patients (delE746-A750 in exon 19, L858R in exon 21) are found in the genes coding for the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR), occurring in 10-30 % of NSCLC patients. Osimertinib, a third-generation EGFR TK-inhibitor (TKI) is a first-line therapy for NSCLC patients harboring activating EGFR mutations (EGFRm). Osimertinib exhibited higher selectivity and lower toxicity than earlier EGFR-TKI's, and targets the acquired resistance mutation (T790M), often emerging in these patients. The current study aimed to develop an 18f-fluorine radiolabeled positron emission tomography probe, based on Osimertinib's chemical structure, to identify EGFRm tumors. Materials and Methods: The non-radiolabeled fluorine-19 reference standard, F-OS was designed via N’-alkylation at a region that is not involved in EGFR binding and was fully characterized. The potency and selectivity of F-OS were evaluated in vitro using the methylene blue IC50 assay and human NSCLC cell lines, of which three possessed different EGFRm (HCC827, NCI-H1975, and NCI-H3255), and one was the wild-type EGFR cell line (QG56). [18F]F-OS was synthesized using a fully automated 90-minute process. In vivo PET/ MRI studies were conducted using xenografts (NCI-H1975 and QG56 cell lines) and analyzed using preclinical image post-processing software. Results: F-OS was obtained at a chemical yield of 20 % (purity > 99%). F-OS binding profile toward the different cell lines (IC50F-OS: HCC827 0.049, NCI-H1975 0.029, NCI-H3255 0.012 and QG56 6.4 µM) were comparable to that of Osimietinib (HCC827 0.002, NCI-H1975 0.004 NCI-H3255 0.004 and QG56 1.8 µM), and corresponded to other reported IC50 values. [18F]F-OS was obtained at a low radiochemical yield (~1 %, radiochemical purity > 99 %, n = 7), yet sufficient for the preclinical PET/ MRI study. [18F]F-OS was evaluated in-vivo PET/ MRI study using NSCLC xenografts harboring EGFRm- (L858R/T790M) or WT EGFR. A significant two-fold accumulation increase in the EGFRm xenografts (n = 5) was observed, contrary to the WT EGFR (n = 3). furthermore, a three-fold tumor/muscle uptake ratio of [18F]F-OS was observed for the EGFRm, compared to the WT EGFR-mice. Conclusion: This study aimed to develop a PET probe for identifying EGFRm-positive NSCLC tumors. F-OS potency and selectivity suggest a comparable EGFR binding profile to Osimertinib. [18F]F-OS accumulation in the EGFRm xenografts warrant improving [18F]F-OS radiosynthesis and performing profound PET/ MRI investigation to elucidate [18F]F-OS potential as a nuclear imaging probe to identify EGFRm tumors.
Onco 7: 18F-FDG PET/CT as comprehensive tool in multiple myeloma
Kartikey P Solanki, Anurag Jain
Department of Nuclear Medicine, Command Hospital, Lucknow, India
Introduction: This study aimed to characterize the 18F-FDG uptake pattern in Multiple Myeloma (MM) patients, assess bone marrow involvement using MRI, and compare the diagnostic utility of 18F-FDG PET/CT against MRI. Materials and Methods: The study included 52 MM patients from a tertiary care government hospital. Initial evaluations gathered clinical histories, biochemical data, and divided patients into pre- and post-therapy groups. MRI was performed for anatomical localization of bone lesions. PET/CT scans were conducted using 18F-FDG. Findings from PET/CT and MRI were analyzed and compared. Statistical tests assessed sensitivity, specificity, PPV, NPV, and accuracy. Results: No significant difference was observed in detecting bone lesions between PET/CT and MRI, with PET/CT demonstrating a sensitivity of 83.3%, specificity of 75.0%, PPV of 88.2%, NPV of 66.7%, and an accuracy of 80.8% when compared to MRI. Discordant results were observed, where PET-CT normalized earlier than MRI in post-therapy patients. Additionally, PET/CT identified lesions outside MRI's field of view and extra-medullary lesions in eight patients, offering an advantage over MRI. Conclusion: This study found no significant difference in detecting bone lesions between whole-body PET/CT and MRI in MM patients. However, PET/CT identified lesions outside MRI's field of view and extra-medullary lesions, offering an advantage over MRI. PET/CT is a valuable clinical tool for comprehensive screening of myelomatous lesions, including both medullary and extra-medullary lesions.
Onco 8: Exploring the spectrum of NET on molecular imaging - Our institutional odyssey with 68Ga DOTANOC and 18F FDG scan
M. G. Vishnoi, I. P. Dubey, Anurag Jain, Satish Vempa, Neeraj Kumar, K. P. Solanki, A. V. S. Anil Kumar
Department of Nuclear Medicine, Army Hospital Referral and Research, New Delhi, India
Introduction: Neuroendocrine tumors (NETs) are a diverse group of neoplasms that arise from neuroendocrine cells in various organs throughout the body. Accurate imaging plays a crucial role in their diagnosis, staging, and treatment planning. This case series aims to demonstrate the value of Positron Emission Tomography-Computed Tomography (PET-CT) scans in the management of neuroendocrine tumors originating from different organs. NETs occur more often in lungs, gastrointestinal tract, or pancreas. NETs in other locations are rare and they have been reported primarily as case reports. We present a collection of cases where PET-CT scan findings provided valuable information about location, metabolic activity and grades of tumors. These informations are useful in deciding patient management. Materials and Methods: We conducted a retrospective observational study during last 06 months at our institute. We received 26 patients of NET. Patients were subjected to metabolic imaging in form of 68Ga DOTANOC scan and 18F FDG PET CT Scan according to tumor grade, differentiation and Ki-67 index values. Patient demography, clinical features, (symptoms, tumor location), histological features (atypia, architecture, mitosis, Ki-67 index), immunohistochemical analysis, tumor grade and metabolic activity were assessed. All cases were independently reviewed by two nuclear medicine physicians and disagreements were solved by consensus. Grading of NETs was done according to the latest WHO classification of Gastroenteropancreatic NETs. Results: There were 12 (46%) male and 14 female (54%) patients. Their ages ranged from 23 to 78 years (mean age 48). 11 tumors (42%) were originating from the gastrointestinal tract, 03 (11.5%) in pancreas, 02 each in lung, prostate & liver and one each in nasal cavity, ovary, breast, gall bladder and mediastinum. We also received one patient of metastatic NET (liver, lung, skeletal and lymph nodal metastases) with unknown primary. We had 07 cases of NET Gd I, 11 of NET Gd II, one of NET Gd III and 06 cases of NEC. All the cases were synaptophysin and chromogranin A positive. Somatostatin receptor activity of tumors ranged from SUV Max 4.2 to 103.2 on 68Ga DOTANOC scan and metabolic activity on 18F FDG scan ranged from SUV Max 8.9 to 12.2. FDG PET CT scan were performed for patient with high grade NET and NEC, in these patient metabolic activity in FDG PET CT scan was higher than SSTR expression. All the cases of NEC were metastatic with most common site being lung, followed by liver, lymph nodes and skeletal system. On analysis of Ki67, metabolic activity and somatostatin receptor expression, our study is in concordance with NET PET scoring system. Conclusion: Our study delved into the spectrum of molecular imaging with use of 68 Gallium and 18 FDG scans in NETs. We analyzed molecular and histological characters of NETs of different grades and few cases of Neuroendocrine Carcinoma. Our findings align with the established NET PET scoring system, validating the efficacy of molecular imaging in NET assessment. This study highlights the versatility of molecular imaging techniques across a wide grades of NETs and demonstrates its invaluable role in the staging, management and response assessment of neuroendocrine tumors. It is also helpful in guiding the site of biopsy. PET-CT imaging plays a vital role in improving patient outcomes and facilitating personalized therapeutic approaches in neuroendocrine tumor management. We have few cases of rare site of origin. These are heterogeneous, and their behavior does not seem to correlate absolutely with tumor grade. More studies are needed to clarify the role of proliferation rate in these tumors.
Onco 9: Exploratory analysis of 64CuCl2 PET-CT imaging in carcinoma prostate and its comparison with 68Ga-PSMA-11 and 18F-FDG PET-CT
Aamir Nazar, Ashwini Kalshetty, Rubel Chakravarty, Sudipta Chakraborty, Sandip Basu
RMC, BARC, HBNI, Mumbai, Maharashtra, India
Introduction: Prostate cancer is the most commonly diagnosed male malignancy and the fourth leading cause of cancer death in men worldwide. There are multiple imaging modalities available for imaging cases of carcinoma prostate with multiparametric MRI and 68Ga-PSMA-11 PET-CT being the most widely used modalities. Even though there are multiple options available for imaging cases of carcinoma prostate there are still areas which require improvement. The role of copper in tumour growth has been demonstrated in multiple studies. There are few pre-clinical studies showing uptake of copper by cells of carcinoma prostate which was followed up by clinical studies where 64CuCl2 PET-CT was compared to multi parametric MRI, 18F-choline PET-CT and 64Cu-PSMA PET-CT which have demonstrated the potential of 64CuCl2 PET-CT to be used for imaging cases of carcinoma prostate. The absence of renal excretion of the tracer and future theranostic potential were the proposed advantages of 64CuCl2 as a PET tracer. So, in this study we evaluated the feasibility of 64CuCl2 PET-CT in evaluating cases of carcinoma prostate and compared it head-to-head with 68Ga-PSMA-11 PET-CT. Materials and Methods: We prospectively evaluated 50 cases of biopsy-proven carcinoma prostate belonging to the entire spectrum of disease of which 21 were for initial staging and 29 were for restaging/response evaluation. Both 64CuCl2 and 68Ga-PSMA-11 PET-CT were done in all patients and 18F-FDG PET-CT was done in patients whenever possible. All the scans were done within a period of 2 weeks. 64CuCl2PET CT was acquired at 1 and 3 hours. We evaluated physiological uptake of 64CuCl2, correlated the uptake in primary disease with disease parameters like Gleason score and S.PSA levels, and compared detection rates for primary and metastatic disease with 68Ga-PSMA-11 and 18F-FDG PET-CT. Results: The detection rates of primary disease in staging cases were the same for both 64CuCl2 and 68Ga-PSMA-11 PET-CT and both agents performed equally in detecting extra prostatic disease. There was no statistically significant correlation between the uptake of 64CuCl2 in the primary with Gleason score and S.PSA levels. In the evaluation of metastatic disease, the detection rate of 64CuCl2 PET-CT was 79% for lymph nodes, 77.3% for skeletal metastases and 80.6 % for soft tissue metastases while 68Ga-PSMA-11 PET-CT performed better with detection rates of 99%, 99% and 85.4% for lymph node, skeletal and soft tissue metastases respectively. In 17 patients where 18F- FDG PET-CT was also done, 64CuCl2 PET-CT detected higher local lymph nodes than 18F- FDG PET-CT which was statistically significant, while for soft tissue metastases, 18F- FDG PET-CT detected more metastases than 64CuCl2 PET-CT which was statistically significant. Conclusion: 64CuCl2 PET-CT did not show any added advantage over 68Ga-PSMA-11 PET-CT in the evaluation of local disease or for the assessment of metastatic disease. Even though the absent urinary bladder and ureteric activity provide better contrast for local disease evaluation, it does not translate to increased disease detection when compared to 68Ga-PSMA-11 PET-CT.
Onco 10: Impact of 18F-FDG PET-CT in baseline staging of Hodgkin's lymphoma: An Indian scenario
Siddharth Sharma, Manish Ora, Sanjay Gambhir
Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: Lymphomas can affect any organ in the body and present a wide range of symptoms. They are traditionally divided into Hodgkin's lymphoma and Non-Hodgkin lymphoma. Most patients with Hodgkin's lymphoma(HL) present with constitutional symptoms and supra-diaphragmatic lymphadenopathy. Retroperitoneal and inguinal lymphadenopathy occur less frequently. Currently, recommended approaches for determining clinical stage consist of routine physical examination, laboratory analysis including assessment of renal and hepatic function, chest x-ray; CT scans of the chest, abdomen, and pelvis; and bone marrow biopsy for any extent of disease beyond the clinical stage. 18F-FDG PET is included in the most recent National Comprehensive Cancer Network (NCCN) staging recommendations for pre-treatment evaluation, particularly in the setting of equivocal CT scan results. We aimed to examine the impact of staging positron-emission tomography/computed tomography (PET-CT) in Hodgkin's lymphoma. Materials and Methods: We retrospectively examined our department's database for the histologically proven cases of Hodgkin's lymphoma who underwent 18F-FDG PET-CT for staging from January 2021 to Dec 2022. Standard preparations for 18F-FDG PET-CT were performed, and image acquisition was made using a Siemens Biograph PET-CT scanner. Experienced and certified nuclear medicine physicians independently evaluated all 18F-FDG PET-CT images. All scans were evaluated for non-physiological FDG uptake. Based on PET-CT findings, the staging category was done as per the Cotswolds-modifies Ann Arbor classification. Results: A total of 110 patients were included in this study. The mean age of the patients was 24.4 years + 18.6 years, comprising 71.5% males and 28.5% females. Patients aged less than 20 years were 46.7%, those between 20-59 years were 46.7%, and > 60 years was 6.6 %. Based on 18-F-FDG PET-CT findings, stages I and II were seen in 14.6 % and 8.2 % of patients. Stage III and IV were seen in 40.3% and 36.6%, respectively. Patients presenting with an advanced stage (III and IV) were more than three-fourth (76.9%) of the total number of patients. Splenic involvement was seen in 54.5% of patients with stage III. Marrow involvement was seen in 42.5 % of patients with Stage IV disease. Conclusion: Our study suggests that late clinical presentation with advanced stage is prevalent in the Indian population. Management based on regional computed tomography may underestimate staging in many patients. It could result in undertreatment and poor prognostication. In the Indian scenario, splenic and bone marrow involvement is not uncommon and could be missed in anatomical imaging modalities. Anatomical modality may miss the normal size lymph nodal involvement. Investigations are cheaper in developing nations, especially in India, where PET-CT costs Rs.8000- 25000. Whole-body PET-CT could be more cost-effective than multiple CT scans (Rs. 3000-4000 each) and bone marrow evaluation (Rs. 4000-8000). 18F-FDG PET-CT imaging upfront during baseline staging accurately stages the patients. It allows interim treatment response evaluation and guides management.
Onco 11: Role of sFDG PET/CT in adrenocortical carcinoma - A retrospective single center experience
Chandrasekaran G, Jasim Jaleel, Madhavi Tripathi, Nishikant A. Damle, Rakesh Kumar, Chandrasekhar Bal
Department of Nuclear Medicine, AIIMS, New Delhi, India
Introduction: Adrenocortical carcinoma (ACC) is a rare malignant neoplasm of the adrenal cortex that has a poor prognosis because of its aggressive nature, rapid pace of disease progression and high recurrence rates. The only possibly curative treatment for ACC is a complete surgical resection. For unresectable disease, chemotherapy or mitotane or both are the only treatment options. Here we explore the role of FDG PET/CT in pre-operative staging, post-operative/post-treatment response assessment and follow-up of patients with adrenocortical carcinoma. Materials and Methods: Data of consecutive patients (both pre-operative and post-surgical status) with histopathologically proven ACC, who underwent 18F-FDG PET/CT in our department from January 2017 and August 2023 were retrospectively assessed. The PET/CT scans were analyzed by two experienced nuclear medicine physicians. For the patients who underwent follow up scans, the response categories were recorded as progressive disease (PD), stable disease (SD), partial response (PR) and complete response based on PERCIST 1.0 criteria. Results: Forty-six (46) patients were included in our study, twenty (20) patients were treatment naive (males = 16, females = 4) with mean age of 41.9 years and twenty-six (26) patients were post-operative (males = 15, females = 11) with mean age of 34.5 years. Of the treatment naive patients, seven (35%) had disease localized to the involved adrenal gland (right = 5, left = 2), while the disease was upstaged by PET-CT in thirteen (65%) patients. Among the patients who had metastases, three had only retro-peritoneal lymph node involvement, while one, three and seven patients had metastases to contralateral adrenal, liver and lungs respectively. In the patients who underwent post-operative imaging (26), PET-CT revealed no evidence of residual disease in five (19.2%) patients, while fourteen (53.8%) patients had residual disease and seven (26.9%) patients had disease recurrence. Among the patients who had residual disease, the common sites of involvement were post-operative region (6), retro-peritoneal lymph nodes (6), bone (4), lungs (3), liver (1) and brain (1). Further follow-up FDG PET/CT in these patients revealed disease progression in six (42.8%), stable disease in one (7%), while six (42.8%) were lost to follow up and only one patient achieved complete metabolic response. In the patients who had recurrence, the common sites of disease relapse were the lungs (4), post-operative region (3), liver (2) and retro-peritoneal lymph nodes (1). On follow-up of these patients with disease recurrence, one (8.3%) had stable disease and two (28%) had disease progression, while four patients were lost to follow up. Conclusion: In patients with adrenocortical carcinoma, PET/CT could play an important role in evaluation of disease extent at baseline, in post-operative patients it could help in evaluating for residual disease, disease recurrence and assessment of treatment response.
Onco 12: Exploring human physiological biodistribution of 64-copper chloride (64CuCl2) and further comparison of 64CuCl2 with 18-fluorodeoxyglucose PET-CT in various malignancies
Parth Baberwal, Sunita Sonavane, Rubel Chakravarty, Sudipta Chakraborty, K. V. Vimalnath, Sandip Basu
RMC, BARC, HBNI, Mumbai, Maharashtra, India
Introduction: Copper ions are necessary for many biological processes in the human body and are essential for life. Liver is the principal organ that regulates the status and convergence of copper particles in the body. By utilizing the simultaneous emission of both - (37.1%) and + (17.9%) particles (for PET imaging and therapy) with T1/2 = 12.7 h, simple 64Cu ions can be used as theranostic agent. Interesting to note that this therapeutic potential is further increased by the amount of its decay that occurs by electron capture (EC, 43.5%), which promotes the emission of Auger electrons which have high linear energy transfer (LET). These proposed benefits and theoretical advantages of copper have been studied upon in our study and evaluated if they translate into clinical application. Present era most commonly utilized radiotracer in oncologic disease imaging procedures employing positron emission tomography–computed tomography (PET-CT) technology is 18FDG. 18FDG imaging is commonly indicated for cancer imaging, aiding in initial diagnosis, staging the disease in a recently diagnosed malignancy, restaging the disease post-therapy and in long term follow-up surveillance. The current study aimed to evaluate the biodistribution and potential of 64CuCl2 PET and quantify its uptake by maximum standard uptake value (SUVmax) in a range of primary, metastatic, or recurrent malignancies and compare the same parameters for 18FDG-PET. Materials and Methods: Fifty-three patients diagnosed with various biopsy proven malignancies (except prostate cancer which was included in a different study) were recruited in this prospective study. All patients underwent both 64CuCl2 and 18FDG PET/CT. 64CuCl2 PET/CT was acquired at 1-hour, 3-hour and 24-hour time points. We studied the human physiological biodistribution of 64CuCl2 in the various organs, corroborated uptake of 64CuCl2 with various types of malignancies, compared uptake with 18FDG PET/CT and correlated with each other in various lesions. Results: The biodistribution study showed that liver was concentrating 64CuCl2 the most out of all the organs, followed by pancreas and large intestine. Liver and intestinal activity increased subsequently with delayed imaging, while washout of 64CuCl2 was noted in pancreas in delayed images and followed a hepatobiliary excretion of tracer over a period. In lesion-wise analysis, it was noted that primary of NET, melanoma and renal/urothelial malignancy group showed more uptake of 64CuCl2 than that in metastasis and vice-versa was noted in lung and soft tissue malignancies. Comparing it with 18FDG, it was seen that FDG showed more uptake in lesions and showed slight correlation (Kappa value: 0.089) with uptake of 64CuCl2 in lesion-wise comparison. Conclusion: Biodistribution studies showed liver as the organ with maximum uptake which implies it may hinder detection of abdominal/hepatic disease and may hamper its potential of its usage as a therapeutic agent. 64CuCl2 PET/CT did not show any added advantage over 18FDG-PET/CT in evaluation of various primary and their metastasis.
Onco 13: Radiolabeling methods in the preparation of 89Zr-PSMA-617 and its physicochemical evaluation
M. K. Ray, Ashok Chandak, Ankita Jadhav, Monica Dubey, K. Kushwaha, M. K. Ray, Sandip Basu
Radiation Medicine Centre, BARC, Mumbai, Maharashtra, India
Introduction: Positron emitters like 89Zr with a long half-life would provide advantages in terms of the ability to predict the radiation doses of normal tissues and organs at later time point. It is advantageous to compare them to the doses that are required to induce toxicity in metastatic castration resistance prostate cancer (mCRPC) during PSMA radiotherapy. PET scans using 68Ga-PSMA-617 should be performed within a few hours from injection due to the short half-life of 68Ga (half-life: 68 mins). However, radioactivity persists in the urine at this time, which prevents dose optimization of 177Lu-PSMA-617. We assume that the long-lived positron emitter 89Zr (half-life: 3.3 d) would be better than 68Ga-PSMA-617 for optimizing the doses of 177Lu-PSMA-617 and may increase sensitivity by allowing longer clearance from non-target organs. The aim of the present study was to formulate 89Zr-PSMA-617 and evaluate its physicochemical properties. Materials and Methods: 89Zr was produced as at BARC/BRIT Medical Cyclotron by irradiating 89Y foil, sandwiched in between copper plate, with 12 MeV proton beam & 10 µA current for 40 min. Purification of 89ZrCl2 was done using Hydroxamate and QMA(Cl-) column. Labeling of PSMA 617 was done using 30/60/90µg of peptide in HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid)containing DMSO for labeling was used. The labeling was carried out in pH ranging from 5 to 9 and different concentration of DMSO (25µl, 50µl or 100µl). The reaction temperature was set at 900C and reaction time varied from 30 min to 45 min. Volume of reaction mixture was around 700-900µl Radiochemical purity was evaluated by iTLC-SG in citrate buffer (0.1 M; pH 5.0); Rf = 0.0 and MeOH : 1 M ammonium acetate solution (1:1); Rf = 0.7-0.9. The stability of the labeled product was evaluated for 48 hrs. Results: 400 μCi of 89Zr was produced in the medical cyclotron at EOB and 216 μCi of purified 89ZrCl2 was obtained after chemical separation. This was successfully labelled to 60 mg of PSMA-617 in HEPES buffer (pH 7.0) containing 50 µl DMSO and heated for 45 min at 90 0C (reaction volume ~750µl). The RCP of the labeled product was found to be 90 % using the above conditions. The product was found stable up to 24 hr and found degraded after 48 hrs. (RCP was below 50 %) at room temperature. Conclusion: This is the first report on the preparation of 89Zr-PSMA-617 from BARC/BRIT Medical Cyclotron Facility. Labeling optimizations of 89Zr with PSMA-617 is still under progress to improve the stability and RCP and suitable for preclinical studies.
Onco 14: A prospective study to establish link between myocardial 18F-FDG PET CT uptake and fasting blood sugar and fasting period of the patient
R. Sowmya, K. K. Kamaleshwaran, E. Ramkumar, E. R. Radhakrishnan, F. R. Kingsley, Arun Pandiyan, M. Sowmya, R. Ruth, Suvalakshmi, R. V. Rithika
Department of Nuclear Medicine, The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India
Introduction: 18F-FDG is a radiopharmaceutical which is used in Positron Emission Tomography (PET) for functional imaging. The mechanism of invivo 18F-FDG uptake is similar to that of glucose as it is a glucose analog. The aim of this study is to co-relate the myocardial FDG uptake in routine PET CT studies with fasting blood sugar and fasting period. Materials and Methods: 18F-FDG PET scan images and their reports were interpreted for 110 patients prospectively. Patients were classified on the basis of myocardial uptake; Grade 0 = no myocardial uptake; Grade 1 = mild uptake(equivalent to normal liver tissue); Grade 2 = moderate uptake (>liver but < brain); Grade 3 = marked uptake (equivalent to brain). Quantitative analysis was done by calculating standardized uptake value(SUV max). Results: On analysis of myocardial uptake of 110 patients, it is found that only one patient (0.9%) showed no uptake in myocardium(Grade 0). Sixty nine(62.7%) patients were rated Grade 1, twenty nine(26.3%) patients were rated Grade 2, seventeen (15.4%) patients were rated Grade 3. The mean value of fasting period, fasting blood sugar level were 6 hour, 121mg% for Grade 1; 6 hour, 107mg% for Grade 2 and 6 hour, 148mg% for Grade 3. SUV max was found to vary between 0-1. Conclusion: The degree of myocardial FDG uptake did not show significant correlation with fasting blood sugar level and fasting period.
Onco 15: Unlocking the secrets of tumour thrombus: Our journey in molecular imaging
I. P. Dubey, Neeraj Kumar, M. G. Vishnoi, J. S. Arora, N. Nidheesh Kumar, A. V. S. Anil Kumar
Department of Nuclear Medicine, Army Hospital Research and Referral, New Delhi, India
Introduction: Tumour thrombus, the presence of tumor cells within vessels, poses a significant clinical challenge. This abstract presents a retrospective analysis of PET/CT scans performed over the past six years at our institution, focusing on the detection and characterization of tumor thrombus in a spectrum of malignancies, including Renal Cell Carcinoma (RCC), Hepatocellular Carcinoma HCC), Testicular Seminoma, Lung Carcinoma, Jugular Foramen Paraganglioma etc. Materials and Methods: We conducted a comprehensive review of PET/CT scans performed between 2017 to 2023 at Army Hospital R&R. The study cohort included approximately 19000 scans for various malignant and non-malignant etiologies. It included the patients diagnosed with the aforementioned cancers. All the PET-CT reports of aforementioned duration were searched with keywords ‘Tumour Thrombus’. A total of 25 reports of 21 patients were found to have mention of the keywords. 17 patients underwent single PET-CT scan whereas 4 patients had undergone a repeat scan for response assessment or follow up. Detailed analysis of PET/CT images by two independent Nuclear Medicine Physicians was performed again to identify and characterize tumor thrombi. Another cohort of 20 patients having bland thrombus was selected to compare and contrast the characteristics with tumour thrombus. Results: Out of 21 patients, 07 cases were diagnosed with RCC while 05 were HCC. The remaining cases had malignancies 01 each from gall bladder, lung, esophagus, testis, uterus, jugular foramen, pleomorphic sarcoma, plasmacytoma and lymphoma. Our study revealed the presence of tumor thrombus in various locations, including the IVC, renal veins, hepatic veins, portal veins, SVC, IJV etc. Direct infiltration of vessel in a linear pattern was the prevailing mode of dissemination. Of particular interest, IVC (38%) were most commonly involved, closely followed by renal veins (28%) and portal vein (24%). Furthermore, standardized uptake values SUVmax) ranged from 3.4 to 30.1 with a mean SUV max of 10.8 as compared to mean activity of 1.9 of mediastinal blood pool. When compared to bland thrombi (mean SUVmax 1.2), metabolic activity was found to be significantly higher in tumour thrombi. It was also observed that unlike tumour thrombi, bland thrombi do not cause structural changes in the involved vessel and they tend involve single vessel with relatively smaller extent. In summary, this study sheds light on the distribution, pattern and metabolic activity of tumour thrombi. Conclusion: Our retrospective analysis of PET/CT scans performed over the past six years demonstrates the utility of this imaging modality in detecting and characterizing tumor thrombus in a variety of malignancies. The metabolic activity, distribution and the patterns of FDG uptake can be helpful in differentiating tumour thrombus from benign thrombus. This information is invaluable for treatment planning and surgical decision-making. Further research is warranted to establish the correlation between the presence of tumor thrombus and patient outcomes.
Onco 16: Peritoneal metastasis: PET/CT a precise imaging modality
Man Mohan Singh, P. Bose Thakur, L. Kakkar, S. Deswal
Department of Nuclear Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: Presentation of peritoneal metastasis is usually clinical and in late stage of disease. It is highly unpredictable and difficult to diagnose mainly based on clinical sign and symptoms. Often peritoneal metastasis is incidental finding detected during surgical exploration or diagnostic imaging workup for other indications. Due to lack of adequate/ satisfactory preoperative detection modalities, accurate incident data is absent. Hybrid imaging like PET/CT provides the anatomical as well as functional data in a single imaging episode. The aim of the study was to detect the peritoneal metastasis in occult/ suspicious patients and recurrence/ response to treatment on follow-up PET/CT. We also want to find out the types of malignancies involving the peritoneum. Materials and Methods: This retrospective descriptive study was carried out in between January 2022 to September 2023. We reviewed the 18F FDG PET/CT scan of 59 patients having peritoneal deposits with histologically proven known primary and unknown primary to know the primary site. All FDG PET/CT images were reviewed by the two independent nuclear medicine physicians with consensus. Results: A total of 59 patient, 33 male (55.9%) and 26 female (44.0%) with a median age of 52 years (range, 23-72 years) were included in this study. Among 59 patients, 57 had known histologically proven primary i.e. 15 ovarian (most common 25.4%), 1 cervix, 2 endometrial, 3 breast, 2 lung, 3 renal, 4 urinary bladder, 1 testis, 1 buccal mucosa, 2 stomach, 9 gallbladder, 2 hepatic, 1 pancreatic, 1 periampullary, 6 colon, 5 anorectum and 1 non Hodgkin's lymphoma) and 2 patients were for unknown primary site for biopsy. In these 2 patients of unknown primary, PET/CT precisely told the primary site (one having gallbladder and second having ovary) and peritoneal metastasis. In total of 59 patients, 11 (18.6%) patients of occult/ clinical suspicious for peritoneal deposits, PET/CT precisely detected peritoneal involvement. 4 (6.7%) patients having known for peritoneal deposits on USG/CT and rest of 44 (74.5%) patients having unavailable prior data were positive on PET/CT. PET/CT scan precisely told the recurrence in 2 (3.3%) patients in the form of peritoneal deposits and response to therapy in 17 (28.8%) patients (according to PERCIST criteria) on follow-up. A total 17 patient, 2 had complete metabolic response, 2 had partial response, 2 had stable disease and 11 had progression of disease. Rest of the 40 (67.7%) patients were staged/ evaluated for disease status on PET/CT. Conclusion: PET/CT is a precised hybrid imaging modality for diagnosis, staging, restaging, response evaluation, recurrent/ residual disease and surveillance of peritoneal metastasis.
Onco 17: Non-invasive detection of tumour-stroma ratio from 68Ga-FAPI PET/CT images of colorectal carcinoma using machine learning on standardized uptake values
N. Varghese, H. Varatharajan, L.G. Reddy, K. Sekar, P. Khobragade, N. Varghese, A. Shanker
Department of Nuclear Medicine, Siemens Healthcare Private Limited, India and Health Care Global Private Limited, Bengaluru, Karnataka, India
| Metric | Training Dataset (n=60) | Test dataset (n=23) |
|---|---|---|
| Accuracy | 88.3% | 86.9% |
| Sensitivity (True positive rate) | 72.7% | 83.3% |
| Specificity (True Negative rate) | 97.4% | 88.2% |
| Precision (Positive Predictive Value) | 94.1% | 71.4% |
| Negative Predictive Value | 86% | 93.7% |
| FI score | 0.82 | 0.77 |
| SUV Max | SUV Mean | SUV Min | Ground Truth | Prediction Probability | Correctness of Prediction Low Stroma P<0.5 High Stroma P≥0.5 | |
|---|---|---|---|---|---|---|
| 1 | 9.2 | 5.3 | 3.6 | High Stroma | 1 | ✓ |
| 2 | 12.4 | 6.6 | 4.9 | High Stroma | 1 | ✓ |
| 3 | 17.83 | 9.5 | 7.13 | Low Stroma | 0.87 | ⨯ |
| 4 | 9.3 | 5.5 | 3.7 | High Stroma | 0.62 | ✓ |
| 5 | 17 | 9.6 | 7 | Low Stroma | 0 | ✓ |
| 6 | 10.1 | 5.9 | 4 | High Stroma | 0.93 | ✓ |
| 7 | 12 | 6.5 | 4.8 | Low Stroma | 0 | ✓ |
| 8 | 12.4 | 6.7 | 4.97 | Low Stroma | 0.34 | ✓ |
| 9 | 16.4 | 8.55 | 6.59 | Low Stroma | 0.27 | ✓ |
| 10 | 18.77 | 10.49 | 7.59 | Low Stroma | 0 | ✓ |
Introduction: The Tumor Microenvironment (TME) in CRC causes resistance to treatment and impacts treatment response, yet TNM guidelines overlook it. TME includes cells like fibroblasts, endothelial, and immune cells. The proportion of stroma in TME is a proven prognostic marker for solid epithelial malignancies. Stroma causes treatment resistance due to its stiff mesh-like barrier nature. Stroma can be assessed adequately in post-surgical resection samples and not at the time of diagnosis due to tumor heterogeneity and inadequate sampling during biopsies; this warrants a need for non-invasive detection of stroma at the time of cancer detection. FAPI PET/CT has been chosen as the imaging modality since it targets cancer-associated fibroblasts (CAFs) that comprise stroma. Since SUV quantifies the concentration of a radiopharmaceutical tracer of the metabolic activity in the lesion, this study aims to find a meaningful correlation between SUV and stromal content in the TME. Materials and Methods: After ethical clearance, a retrospective, cross-sectional study was conducted in HCG Cancer Hospital, Bengaluru involving 83 patients (2019-2023) who had undergone FAPI PET/CT and surgical resection. SUV measurements (Maximum, Minimum, Mean) were carried out on Syngo.via software from SIEMENS. The stromal content was quantified by pathologists on post-surgical resection samples. Multivariate Logistic regression analysis (Supervised Machine Learning) was performed on the training dataset (n = 60) to classify high and low stroma using SUVmax, SUVmin and SUVmean. The classifying model was validated on the test dataset (n = 23), and the discriminative ability was evaluated using performance metrics. Results: The training dataset had 38 low and 22 high stromal content, while the test dataset had 17 low and 6 high. The prediction model is highly significant (p <.001, Chi2(3) = 34.52, n = 60) and had excellent discrimination in the training dataset with AUC = 0.89. F1 score is close to 1 - the model can identify true positives and avoid false positives and false negatives. The sigmoid function obtained with Logistic regression gives the probability of the input variables belonging to either stroma low (P = <0.5) or stroma high (P ≥ 0.5).


Observed vs Predicted Stroma for datapoints plotted in Figure 2. Blue dots are predicted probability of low stroma class while the orange dots are predicted probability of high stroma class. Red dots are false predictions. Conclusion: In this study, we observed a significant correlation (p < 0.001) between SUV values from FAPI PET-CT images of CRC and stromal content. This marks the first-ever study to link FAPI PET/CT-derived SUV with stroma. Establishing a validated biomarker for stromal content holds promise for enhanced prognosis, risk assessment, treatment adjustments including neoadjuvant therapy, immunotherapy response, and personalized radiation dosing. Our forthcoming prospective study will further investigate this correlation using the established model.

| Training Dataset (n=60) | Predicted Low Stroma | Predicted High Stroma |
| Observed Low Stroma | 37 | 1 |
| Observed High Stroma | 6 | 16 |
| Test Dataset (n=23) | Predicted Low Stroma | Predicted High Stroma |
| Observed Low Stroma | 15 | 2 |
| Observed High Stroma | 1 | 5 |
Onco 18: Impact of dual tracer study to differentiate malignant versus benign peritoneal diseases
Vindhya malasani, Swagat Dash, Shreya Dang, Dinesh Pendharkar, Abhishek Raj, Shantanu Chaudhary
Department of Nuclear Medicine, Sarvodaya Hospital, Faridabad, India
Introduction: F18- FDG PET CT scan was the standard imaging modality for detecting peritoneal diseases. However, it is absolutely not tumor specific. To overcome this problem, Ga68 labeled FAPI-46 (fibroblast activation protein inhibitor) was developed. Lilan Fu, Shun Huang et al. showed that the sensitivity for peritoneal detection is around 93.2% by FAPI vs 53.8% by FDG. Aim: we aim to look for the utility of dual tracer study to differentiate benign from malignant pathologies. Methods: All the oncological patients who had indeterminate or negative findings in F18 FDG PET CT scan underwent Ga 68 FAPI-46 PET CT scan. Results were grouped into 4 categories based on quantification marker SUV (maximum standardized uptake value). Category I: likely benign (FDG positive & FAPI negative or both negative), II : Probably benign (both positive but the SUV of FAPI is ≤ 50% of SUV of FDG), III: indeterminate (both positive with SUV of FAPI ranging from 50-70 % of SUV of FDG), IV: likely malignant (both positive with SUV of FAPI >70% of SUV of FDG or only FAPI positive). Histopathology or follow-up imaging served as the standard for the final diagnosis. Results: We have included a total of 30 patients who had indeterminate findings in F18 FDG PET CT scan. Of these, 4 patients were being evaluated for residual/ recurrent disease. Likely Benign Category: All the 6/30 patients were true negative for malignancy; hence FAPI-46 scan alone helped in preventing false positive findings in these patients. Probably Benign Category: 4/30 patients in this category were true negative for malignancy; there by showing that dual tracer indeed additionally helped in reducing false positive rate. Indeterminate Category: 6/30 patients in this category, of which 3 (3/6) were malignant histopathologies including serous cyst-adenocarcinoma ovary and endometrial carcinoma and rest 3 (3/6) were benign (tubercular and inflammatory). Likely Malignant Category: Remaining 14/30 patients were true positive for malignancy. In 2/14 patients who were histo-pathogically proven to have signet ring variant of adenocarcinoma stomach, FAPI-46 PET CT scan alone could detect primary and metastatic disease; hence reducing false negative rate. Additionally, FAPI-46 PET CT scan also helped in effectively detecting primary mitotic lesions in 4/14 patients with histopathology of adenocarcinoma colon, stomach and ovaries. Rest 8/14 patients had positive findings in both the scans, with 2 (2/8) patients positive for residual disease post-surgery, 2 (2/8) with proven recurrent peritoneal disease and remaining 4/(4/8) patients were treatment naive. Conclusion: From the literature survey, we found neither FAPI -46 nor FDG were absolutely tumor specific. But it is already proven that Ga68 FAPI-46 PET CT scan has definitely surpassed F 18FDG PET CT scan in case of sensitivity. In this study, we have found that using dual tracer helped in differentiating benign from malignant thereby, reducing false positive and negative rates in peritoneal diseases. Our major limitation however, was the low study population; thus further studies with larger population groups are required.
Onco 19: Role of interim FDG PET/CT (iPET) scan in response assessment in paediatric Burkitts lymphoma
Suchismita Ghosh, Sneha Shah, Nilendu Purandare, Archi Agarwal, Venkatesh Rangarajan
ACTREC, Tata Memorial Centre, Mumbai, Maharashtra, India
Introduction: Burkitt lymphoma (BL) is a highly aggressive B cell non-Hodgkin lymphoma. Average age of diagnosis in paediatric patients is 3 to 12 years. It is often associated with Epstein-Barr virus(EBV) infection. WHO has categorized it into 3 clinical variants- endemic BL, sporadic BL and immunodeficiency associated BL. While most common site of endemic BL is jaw bone, sporadic BL generally presents with an abdominal mass. It is extremely sensitive to chemotherapy, with survival ranges from over 80 to 50% related to the stage and age of diagnosis. FDG PET/CT is a routinely used imaging modality for staging of BL. Owing to the high cell-turnover, almost all cases of BL are FDG avid. However, its role in treatment response and its effect on prognosis is an area which needs to be explored more. Materials and Methods: Patients were retrospectively identified with histological proven BL between January 2015 and December 2020. All those who had a baseline and an interim FDG PET/CT were included in the study. Patients with a Deauville score (DS) of 1,2,3 on iPET scan was considered as complete response and negative for residual disease whereas a DS 4,5 was considered positive for residual disease. The PET results were corroborated with histology or follow up. Diagnostic accuracy of PET response was calculated with sensitivity, specificity, Positive predictive value and Negative predictive value. Results: The sample size of this study is 40 which includes 32 male and 8 female patients. All of them had a baseline and an interim FDG PET/CT. 28 patients had a positive iPET scan while 12 patients had negative scan. Out of these 28, 14 patients each had a DS of 4 and 5, respectively. Out of the 12 patients, only 1 had a DS of 1, 3 had a DS of 2 and 8 had a DS of 3. Only one of the patients underwent surgery after chemotherapy. Rest all patients received maintenance chemotherapy and underwent end of treatment PET(eotPET) scan to look for response. 21 patients had positive iPET scan wherein the disease later responded to treatment (true positive) while 7 had false positive iPET scan. 10 patients had a negative iPET scan and remained disease free (true negative), while 2 patients had a negative scan (DS 3), however progressed on further treatment. Thus, the sensitivity, specificity, PPV and NPV were 91%, 59%, 75% and 83%, respectively. Conclusion: FDG PET/CT and Deauville 5-point scale are routinely used for lymphoma response assessment, however, in Burkitts lymphoma which majorly involves the intestinal loops, DS underestimates the response giving rise to a significant number of false positives. This reduces the specificity and PPV significantly. Simultaneous assessment of the CT component for mucosal inflammatory post-treatment FDG uptake can reduce false positive results and avoid overt-treatment, if any.
Onco 20: To evaluate the correlation between d'amico risk stratification and value of SUVmax F-18 PSMA PET CT in newly diagnosed prostate cancer
Meet Patel, Priya Sharma, Gurudas Singh, Shubham Dadhich, Ram Singh Meena, Karan Peepre
Department of Nuclear Medicine, Mahatma Gandhi Medical Collage and Hospital, Jaipur, Rajasthan, India
Introduction: Prostate cancer is the most common male malignancy and the third leading cause of cancer death in men. The introduction of prostate specific membrane antigen positron emission tomography/computer tomography (PSMA PET-CT) has improved the detection of loco-regional and metastatic disease. PSMA PET-CT also plays an important role in the primary diagnosis and staging of prostate cancer patients. In this study, we aim to evaluate the correlation between the intensity of PSMA expression by 18F-PSMA-1007 PET/CT and the D’Amico risk classification of newly diagnosed prostate cancer patients. Materials and Methods: The PET/CT images and data of 30 newly diagnosed prostate cancer patients were analyzed retrospectively, who underwent 18F-PSMA-1007 PET/CT between April 2021 and September 2023. Maximum standardized uptake values (SUVmax) were calculated by drawing region of interest (ROI) for the primary lesions. The correlation between the SUV max value and D’Amico risk classification, as well as Gleason score (GS) grade group and serum prostate specific antigen (S.PSA) level, was evaluated using Pearson correlation test (r). Results: Most of the patients (23 patients, 76.67%) were in the high-risk D’Amico risk classification. The mean SUVmax values of the primary tumour for all patients were 23.023 ± 16.04. The SUVmax values for low and intermediate-risk patients (mean 14.55+ 8.65) & High-risk patients (mean25.60+17.65). No significant or very weak correlation was found between SUVmax values with the D’Amico risk classification (r = 0.25 and p-value = 0.91), as well as Gleason score (GS) grade group(r = 0.24 and p-value = 0.90) and serum prostate specific antigen (S.PSA) level(r = 0.20 and p-value = 0.90). Conclusion: PSMA expression in primary tumour is not significantly correlated with GS grade groups, S.PSA level and D’Amico staging. Therefore, 18F-PSMA-1007 PET/CT might not be a suitable parameter for risk stratification of prostate cancer patients. One of the limitations of study was small sample size of patients.
Onco 21: Overview of 2.5 years’ experience of 68Ga-DOTA-FAPI04 and 68Ga-DOTA-FAPI46: optimization of radiolabelling protocol and assessment of its in-vitro performance parameters
B. S. Shetye, H. Pise, V. Rangarajan
Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Mumbai, Maharashtra, India
Introduction: Fibroblast activation protein (FAP) is a type II transmembrane serine protease. FAP is overexpressed in cancer-associated-fibroblasts but not in normal tissues. FAP is highly expressed in the stroma surrounding more than 90% of epithelial-derived tumours and their metastases. FAPinhibiters (FAPI) have emerged as molecular targeting imaging probe in oncology. Various FAPI derivatives like FAPI04, FAPI34, DOTA.SA.FAPI, FAPI46 etc. based on chemical modification of quinoline group are available. Earlier we used FAPI04 for patient studies and latter we switched over to FAPI46. Aim of our study to evaluate the pharmacokinetic parameters of FAPI04 and FAPI46 in routine use. Materials and Methods: 68GaCl3 was obtained from ITG 68Ge/68Ga generator using 0.05M HCl as an eluent. Radiolabelling was performed manually with 0.25M sodium acetate. Radiosynthesis were performed using FAPI04 (n = 106), FAPI46 (n = 30). Earlier 33 µg (n = 28) and 50 µg (n = 5) of FAPI04 was used to optimize the peptide content for synthesis of 68Ga-DOTA-FAPOI04. Synthesis of 68Ga-DOTA-FAPI46 was performed using 33 µg of peptide. Peptide was preheated at 950C followed by elution with 0.05M HCl. Mixture was heated for 10 min at 950C, loaded on a preconditioned C-18 cartridge, eluted with 70% ethanol followed by saline and filtered through 0.22µ Millipore filter. Physical appearance, pH and colour of the labelled product and waste were assessed. Radiolabelled yield and RCP of the product was assessed by HPLC (gradient method) and TLC using 0.1M sodium citrate and 50% acetonitrile as solvents. Stability was determined till 4 hrs by ITLC method. In vitro serum stability was assessed at 30 min, 1 hr and 2 hrs by ITLC method. Results: Labelled product 68Ga-DOTA-FAPI04 and 68Ga-DOTA-FAPI46 were found to be colorless, non-turbid with pH of 5. Radiolabelling yield of FAPI46 was 85.89% ± 1.9 and for FAPI04 was 84.26% ± 2.2 with 33 µg and 85.45% ± 2.8 with 50 µg of peptide. FAPI04 and FAPI46 showed stability as 96.31% ± 2.8 and 97.19% ± 3.2 at 4 hrs. In-vitro serum stability test (n = 2) at 30 min, 1 hr and 2 hrs showed RCP as 98. 16%, 97.89% and 97.21%. Conclusion: Our study showed 33µg of peptide as optimum quantity for synthesis. Both FAPI04 and FAPI46 showed similar results for performance parameters like RLY, RCP and stability. Hence, both 68Ga-DOTA-FAPI04 and 68Ga-DOTA-FAPI46 can be used as a choice of tracer for evaluation.
| RCP by TLC | 68Ga-DOTA-FAPI04 (%) | 68Ga-DOTA-FAPI46 (%) | ||||
|---|---|---|---|---|---|---|
| 30 min | 1 h | 2 h | 30 min | 1 h | 2 h | |
| 0.1MNa citrate | 98.84±0.7 | 98.27±0.81 | 97.18±1.5 | 99.1±0.69 | 98.93±0.71 | 98.1±0.98 |
| 50% acetonitrile | 98.24±0.86 | 97.84±0.98 | 96.89±1.1 | 98.89±0.82 | 98.45±0.79 | 96.24±0.91 |
| RCP by HPLC | 100 | 100 | 100 | 100 | 100 | 100 |
HPLC: High performance liquid chromatography, RCP: Radiochemical purity, TLC: Thin layer chromatography
Onco 22: Feasibility studies for radiolabeling: Using clinical grade [64Cu]CuCl2 produced by (p,n), (n,p) and (n,γ) routes
R. T. Nimmagadda, S. Sahu, S. Lad, K. Kushwaha, A. Chakraborty, A. Mitra, M. K. Ray, S. Basu
Radiation Medicine Centre, BARC, Mumbai, Maharashtra, India
Introduction: Copper-64, by virtue of its simultaneous emission of β+ and β- particles was considered to be an important diagnostic radiotracers and radiotherapeutic agents. In recent years, alternate route for production of clinical grade [64Cu]CuCl2, apart from conventional route using cyclotron via 64Ni(p,n)64Cu nuclear reaction has been reported. This prompted us to evaluate the effectiveness of [64Cu]CuCl2 produced by alternate route namely 63Cu(n,γ)64Cu and 64Zn(n,p)64Cu for radiolabeling of various Copper-64 based radiopharmaceuticals, further compare to that of [64Cu]CuCl2 produced by conventional route via 64Ni(p,n)64Cu. In this study, for evaluating the suitability of [64Cu]CuCl2 for radiolabeling, H2-ATSM was radiolabeled with clinical grade [64Cu]CuCl2 produced from three different routes. Materials and Methods: No carrier added (nca) clinical grade [64Cu]CuCl2 was produced via 64Zn(n,p)64Cu and 64Ni(p,n)64Cu nuclear reactions at fast neutron flux reactor (APSARA-U) and 16 MeV cyclotron (GE PETtrace) respectively. While carrier added (ca) clinical grade [64Cu]CuCl2 was produced via 63Cu(n,γ)64Cu at medium neutron flux reactor (DHRUVA). The formulation of [64Cu]Cu-ATSM (n = 4) was carried out separately using each of the clinical grade [64Cu]CuCl2 produced from three different routes. All the formulations of [64Cu]Cu-ATSM were carried out identically using [64Cu]CuCl2 produced from three different routes. Typical patient doses formulation (~16-17 mCi) of [64Cu]Cu-ATSM was carried out using [64Cu]CuCl2 (~18-19 mCi in 750 µL), 0.2N CH3COONa solution, H2-ATSM (200 µg in 100 µL of DMSO). The reaction mixture was incubated at 28oC for 30 min at pH~5.5. The reaction mixture was loaded on to preconditioned light tC18 cartridges and eluate was sent to waste vial. SPE cartridge was washed with 2.0 mL of saline to remove excess of unlabeled [64Cu]Cu2+. Finally the [64Cu]Cu-ATSM was eluted with 300 µL of 100% ethanol. Post-purification, 4.4 mg of sodium ascorbate was added to [64Cu]Cu-ATSM (~250 µg/mCi). The resultant [64Cu]Cu-ATSM was diluted with saline such that radioactive concentration (RAC) were maintained ~3.0-3.2 mCi/mL and ethanol content in final product was ~5.66%. Finally the [64Cu]Cu-ATSM was filtered using sterile 0.20 µm PES membrane syringe filter. RCP was assessed by radio-TLC (60AoSG, 100% CH3COOC2H5) and radio-HPLC (RP18, 280 nm and 1.0 mL/min). In-vitro saline stability of the product on storage at 4oC was evaluated by radio-HPLC at 6h post-radiolabeling. Results: The observed radiochemical yield (RCY) of the produced [64Cu]Cu-ATSM was ~85% using nca [64Cu]CuCl2 produced from two different routes, while RCY of produced [64Cu]Cu-ATSM using ca [64Cu]CuCl2 was ~15%. However the RCP for each of the [64Cu]Cu-ATSM formulations were >99%. All the three different formulations were stable upto 6h post-radiolabeling with RCP >98%. Conclusion: In stand-alone NMCs with in-house cyclotron, it is feasible to use nca [64Cu]CuCl2 (produced from enriched Nickel-64 target) for radiolabeling various Copper-64 based radiopharmaceuticals. However nca [64Cu]CuCl2 produced from fast neutron flux reactor is a preferred choice for centralized radiopharmacies involved in production of various Copper-64 based radiopharmaceuticals and supply to various NMCs across the length and breadth of country like India.
Onco 23: In-house radiolabeling and physicochemical characterization of trivehexin with gallium-68
Karan Tanwar, Dinesh Rawat, Rakhee Vatsa, Vivek Dubey, Abdul Shaikh, Sayak Choudhary, Venkatesh Rangarajan
Advanced Centre for Treatment Research and Education in Cancer, TMC, DAE, Mumbai, Maharashtra, India
Introduction: Among several integrins, avb6 integrin has emerged as a potential biological target involved in various pathological conditions including cancer progression. This study focuses on the in-house radiolabeling, quality control and physicochemical characterization of avb6 integrins targeting trimer i.e., trivehexin with gallium-68. Materials and Methods: For radiolabeling, [68Ga]GaCl3 was eluted with 0.05 M HCl from a 68Ge-68Ga generator. The conjugated trivehexin (25 mg) was incubated with [68Ga]GaCl3 at 95°C for 10 min maintaining the reaction pH ~ 4.5. Post-radiolabeling purification was performed using a C-18 cartridge. The radiochemical yield (RCY) and radiochemical purity (RCP) were determined using radio-thin layer chromatography. In-vitro stability of [68Ga]Ga-trivehexin was assessed in PBS and human serum at 37oC for up to 4 h. The lipophilicity (Log P) of [68Ga]Ga-trivehexin was determined using 1-octanol: saline model. Further in-vitro plasma protein binding of [68Ga]Ga-trivehexin was estimated using trichloroacetic acid precipitation method. Results: The RCY of [68Ga]Ga-Trivehexin was 95% at specific activity of 0.58 mCi/mg. Further, the C-18 purification increased the RCP to more than 99%. In-vitro serum stability assay revealed the stability of the [68Ga]Ga-Trivehexin for up to 4 h with RCP > 95%. The Log P of the product was measured to be – 1.54, indicating the possible involvement of both renal and hepatobiliary excretion. The plasma protein binding of [68Ga]Ga-Trivehexin was found to be 94 %. The high plasma protein binding may result in high blood pool retention. Conclusion: The study demonstrates facile radiolabeling and favourable physicochemical characteristics of [68Ga]Ga-Trivehexin for safe administration in humans, provided that it passes all the required quality control tests. The [68Ga]Ga-Trivehexin has a high potential for use as an imaging agent in malignancies expressing avb6 integrins.
Onco 24: Hopkin's criteria using FDG PET-CT for response assessment and prognostication post neoadjuvant chemoradiation for oesophageal carcinoma
Arun Ravi John, Srivallabh Dande, Jeenu Varghese, C. R. Rakesh
Department of Nuclear Medicine, Command Hospital Air Force, Bengaluru, Karnataka, India
Introduction: Oesophageal carcinoma is an aggressive malignancy with poor prognosis. Neoadjuvant chemoradiation has become a standard treatment approach for esophageal carcinoma, as it aims to downstage the tumor and increase the likelihood of complete resection. However, there is still a need for a standardized and reliable method to evaluate treatment response and predict outcomes in these patients. This study aims to evaluate the effectiveness of Hopkin's criteria in FDG PET-CT for response assessment and prognostication after neoadjuvant chemoradiation in patients with oesophageal squamous cell carcinoma. Materials and Methods: We prospectively evaluated data of patients with histologically proven oesophageal carcinoma with localized disease up to stage IIIA (T stage 1 to 3, N stage 0 to 2, and M0) who underwent neoadjuvant chemoradiation with a curative intent. Serial FDG PET-CTs were done for staging and response assessment, 4 to 6 weeks post therapy. Hopkin's criteria was applied for evaluation of response assessment and follow up PET-CTs by two independent Nuclear Medicine physicians. The uptake in mediastinal blood pool was taken as background for reference. Focal 18F-FDG uptake less than or equal to mediastinal blood pool was scored as 1. Focal 18F-FDG uptake greater than mediastinal blood pool but less than liver was scored 2. Diffuse 18F-FDG uptake greater than mediastinal blood pool or liver was scored 3. Focal 18F-FDG uptake greater than liver was scored 4 and focal intense 18F-FDG uptake significantly greater (more than 2 times) than liver was scored 5. Scores 4 and 5 were reported as positive for residual disease. The same was compared with histopathology report post-surgery or follow up endoscopy at 1year in case of carcinomas in the upper one-third of oesophagus. Chi-square test was used to evaluate agreement between the two reporting physicians and also agreement between the Hopkins criteria for residual disease and histopathology post-surgery or follow up endoscopy at 1 year. Results: A total of 22 patients were evaluated. Mean age of the patients were 60.4 ± 4.6 years. 50% of the subjects were between 50- 59 years, 45.5% were between 60 and 69 years and one was above 70 years. 16 out of 22 patients were males with a Male: Female ratio of 2.6:1. 13 out of 22 patients (59.1%) were reported as positive for residual disease by Hopkin's criteria and 9 out of 22 patients (40.9%) were reported as negative. There was no statistically significant difference (p = 0.57) when both the physicians’ observations were compared. The histopathology report post-surgery and follow up revealed that 14 out of 22 patients (63.6%) were having residual disease and 8 out of 22 (36.4%) as having no residual disease. Hopkin's criteria with a cut off of 3 for residual disease post neoadjuvant chemoradiation had a sensitivity of 92.8%, specificity and PPV of 100%, NPV of 99.6% and accuracy of 99.7%. PET-CT Hopkin's criteria revealed a strong agreement between the Nuclear Medicine physician observations and the histopathology report and follow up endoscopy (P value 0.001). The ROC analysis revealed, the area under curve (AUC) was 0.7 suggesting a strong positive correlation between Hopkins Criteria and histopathology report & follow up endoscopy. Conclusion: Findings of our study suggest that PET-CT reported using Hopkin's criteria with a cut off score of 3 was a robust method with high reproducibility to predict residual disease in patients with carcinoma oesophagus undergoing chemoradiation.
Onco 25: Correlation of 18F FDG PET SUVmax with the cell of origin classification of diffuse large B-cell lymphoma
Sayak Choudhury, Venkatesh Rangarajan, Archi Agrawal, Nilendu Purandare, Sneha Shah, Ameya Puranik, Suchismita Ghosh, Indraja Dev
Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Mumbai, Maharashtra, India
Introduction: Depending on the cell of origin DLBCL can be broadly classified into two groups, Germinal center B –Cell like subtype (GCB) and nonGCB group or Activated B-cell (ABC) subtype. Non-GCB DLBCL is known to be associated with unfavorable prognosis. The most reliable way of differentiating between the two subtypes is via Gene Expression Profiling (GEP), which is rarely done in routine practice due to high cost. Instead, various IHC markers are used as surrogates for DLBCL subtypes. Hans algorithm is one of the most widely used methods that use just three markers, CD10, BCL6 and MUM1 to differentiate between GCB and non-GCB DLBCL. 18F FDG PET is the investigation of choice for staging DLBCL. Studies suggest that various metabolic parameters serve as good prognostic markers. However, correlation between the COO classification and SUV parameters have rarely been investigated and the literature regarding it is pretty scarce. In this study, we aim to see if there is any correlation between SUVmax and COO subtypes of DLBCL as predicted by the Hans algorithm. Materials and Methods: This retrospective observational analysis includes 70 patients who have undergone pretreatment 18F FDG PET/CT in our institute during the period of 2017-2021 and have complete histopathology report(HPR) with full IHC panel available in the Electronic Medical Record (EMR). The scans of the patient were pulled from PACS and reviewed by an experienced Nuclear Medicine Physician, who was blinded to the IHC data. The hottest lesion in each scan was selected and SUVmax was evaluated. Another physician separately collected the HPR data and classified cases according to the Hans algorithm into GCB and nonGCB DLBCL. Mann-Whitney U Test was used to assess the mean SUVmax between GCB and nonGCB DLBCL. ROC analysis and Youden Index was used to find a SUVmax cut off. Chi square test was used to further validate the cut off. Results: Of the 70 patients 18 were stage I, 19 stage II, 20 stage III, 13 stage IV. Patients were classified into GCB and non GCB subtypes equally, 35 each. The median SUVmax between the GCB and non GCB subtypes were 23.7 (range 5.48-50.45) and 29.1 (range 7.25-64.81) respectively. The mean SUVmax between the GCB and non GCB subtypes were 29.54 and 41.46(p value = 0.014; r = 0.3, moderate effect size). Using ROC analysis a SUVmax cutoff of 20 was found (sensitivity = 83%, specificity 43%, AUC = 0.670, p value = 0.014). Using this cut off 73% of the cases with SUVmax <20 were correctly identified as GCB subtype and 60% of the cases with SUVmax > 20 were correctly identified as non GCB subtype (p value 0.019). Conclusion: SUVmax in GCB subtype of DLBCL was found to be significantly higher than that of nonGCB type DLBCL, however the effect size was moderate. Correlation of various IHC markers with other metabolic and PETradiomic parameters may provide more robust data.
Onco 26: Utility of 68-Ga EXENDIN-4 imaging and 68-Ga DOTATATE imaging in evaluation of suspected insulinoma
Harshita Gupta, Vikram R. Lele, Karuna Luthra
Jaslok Hospital and Research Center, Mumbai, Maharashtra, India
Introduction: Insulinomas are the most common cause of endogenous hyperinsulinemic hypoglycemia. These are typically small tumours in the pancreas or, in rare cases, the GI tract. In approximately 25–35% of patients with symptoms and documented hyperinsulinemic hypoglycemia, preoperative localization of insulinomas using MRI/CECT is not possible. Being of neuroendocrine origin, these tumors express peptide receptors, which have been used as molecular targets for radionuclide imaging. These include Somatostatin receptors (SSTRs), Glucagon-like Peptide-1 receptor (GLP-1R), Dihydroxyphenylalanine (DOPA) receptor. The respective radio-nuclide imaging analogues are Ga-68-DOTATATE/TOC, Ga-68-EXENDIN and F-18-DOPA. Benign insulinoma is known to have dense expression of GLP-1R, whereas malignant insulinoma has higher SSTR expression. In addition the more metabolically active or malignant tumors may be detected by F18-FDG imaging. Our objective was to evaluate the utility of 68-Ga-EXENDIN-4 PET/CT for detection of Insulinoma and correlate it with 68-Ga-DOTATATE imaging. Materials and Methods: 40 patients with suspected insulinoma underwent both Ga-68-EXENDIN-4 PET/CT and Ga-68-DOTATATE PET/CT imaging. Patients were injected 3-5 mCi of 68-Ga-EXENDIN-4 intravenously. After 1 hour they were imaged on a 16 slice PET - CT (GE -Discovery IQ 5 ring scanner). Delayed images were acquired at 3 hours where needed. Visual / semiquantitative and quantitative analysis of the scans was performed and Standard uptake values (SUV) normalized to body weight were obtained over the avid lesions. Later patients underwent Ga-68-DOTATATE PET/CT imaging within a month of 68-Ga-EXENDIN-4 imaging. Results: Out of 40 patients, 24/40 showed positive focal uptake on either imaging. 8/40 patients were positive on both EXENDIN and DOTATATE imaging, in which 1 patient with known MEN1 syndrome had multiple lesions (multicentric insulinoma); with both discordant and concordant lesion detection with EXENDIN and DOTATATE imaging. Among these, 7 patients were proven insulinoma, while one showed islet cell hyperplasia. There was discordance among 16/40 patients. 4/16 were positive on DOTATATE but negative on EXENDIN, among these 3 were histopathologically proven insulinoma (1 patient lost to follow up). While 12/16 were positive on EXENDIN and negative on DOTATATE imaging, among these biopsy results available of 9 patients, 8 were positive for insulinoma while one was negative. 16/40 patients were negative on both EXENDIN and DOTATATE imaging for focal uptake; further biopsy/surgery was not performed. However, 4 of these patients, showed diffuse increased uptake on EXENDIN imaging (negative on DOTATATE imaging), clinically better on medical management, with probable diagnosis of adult onset nesidioblastosis. Conclusion: 68-Ga-EXENDIN-4 PET/CT detected larger number of lesions than 68-Ga-DOTATATE PET/CT. However, detection of lesions depends on the molecular nature of the tumors, which may vary with stage of disease and tumor differentiation, and hence we also found lesions which were detected only on SSTR imaging and negative on GLP-1R imaging. In addition there may be heterogeneity of receptor expression in same patient with multifocal tumors (in the setting of MEN-1 syndrome) and therefore both these tracers should be used synergistically.
Onco 27: Targeted homodimeric ligands for enhanced molecular imaging: A comprehensive exploration
Shivani Daksh, Nikhil Kumar, Chandraprakash Gond, Adhithya Anoop, Himanshu Ojha, Anupama Datta
Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Delhi, India
Introduction: Molecular imaging has revolutionized the field of medical diagnostics and research by enabling the visualization and characterization of specific biological processes at the molecular level. This study explores the development and application of targeted multimeric ligands to enhance the precision and sensitivity of molecular imaging techniques. Two prominent multimeric ligands, namely bivalent ligand 99mTc[(EST)2DT] and ¹¹C-(Chal)2DEA-Me, are investigated for their potential in targeted molecular imaging through computational techniques. Materials and Methods: The bivalent ligand 5,8-bis(carboxymethyl)-13-(4-(3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[α]phenanthren-17-yl)-1H-1,2,3-triazol-1-yl)-2-(2-(2-(4-(3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[α]phenanthren-17-yl)-1H-1,2,3-triazol-1-yl)ethylamino)-2-oxoethyl)-10-oxo-2,5,8,11-tetraazatridecane-1-carboxylic acid is a complex structure designed for targeted single-photon emission computed tomography (SPECT) imaging and therapy of estrogen receptor-positive (ER+) tumors. In parallel, we explored a bivalent approach to develop (2E,2′E)-1,1′-((((methylazanediyl)bis(ethane-2,1-diyl))bis(oxy))bis(4,1-phenylene))bis(3-(4-(dimethylamino)phenyl)prop-2-en-1-one) [(Chal)2DEA-Me], a chalcone-based homodimeric ligand for positron emission tomography (PET) imaging of amyloid-beta (Aβ42) plaques after labeling with 11C radioisotope. Results: The radiolabeled complex,99mTc-(EST)2DT was obtained in >99% radiochemical purity and 20−48 GBq/μmol of specific activity. The radiolabeled ligand demonstrated remarkable receptor specificity, leading to a fivefold increase in tumor localization, as indicated by a T/M ratio of 1.11 ± 0.34 at 2.0 hours. This outcome underscores the potential of 99mTc[(EST)2DT] in enhancing the diagnosis and treatment of ER+ tumors. The PET imaging ligand, ¹¹C-(Chal)2DEA-Me demonstrated superior binding affinity compared to monomeric counterparts in the molecular modeling studies and in vitro assessments with synthetic Aβ42 peptide. The radiolabeling process achieved a yield of 40–55% (decay corrected) with specific activity ranging from 65 to 90 GBq/μmol, underscoring the potential of 11C-(Chal)2DEA-Me as an in vivo Aβ imaging tracer. The preliminary analysis indicates high potential of 11C-(Chal)2DEA-Me as in vivo Aβ imaging tracer in comparison to monomeric ligand. Conclusion: The molecular modelling tools have been found to be highly useful tools in understanding the various pathways. This investigation into targeted multimeric ligands represents a promising avenue for advancing molecular imaging techniques. Tailoring ligands to specific molecular targets and harnessing radiolabeling techniques hold the potential to enhance imaging accuracy and specificity, thereby improving patient care and expanding our comprehension of intricate biological processes.
Onco 28: Normal standardized uptake values obtained from quantitative 99mTc HYNIC PSMA-11 SPECT/CT in prostate cancer patients
Ritwik Sinha, Sachin Tayal1, Jay Prakash1, Manoj Chauhan1, M. V. Manikandan1
Department of Nuclear Medicine, 1Homi Bhabha Cancer Hospital (A Unit of TMC), Varanasi, Uttar Pradesh, India
Introduction: Retrospective evaluation of 99mTc HYNIC- PSMA-11 SPECT/CT and understanding its biodistribution in terms of SUV in histologically confirmed prostate cancer patients. Materials and Methods: A retrospective analysis of a 99mTc HYNIC-PSMA-11 scan was done on twenty-four patients. The inclusion criteria were: biopsy-confirmed cases of carcinoma prostate, no previous treatment history to the author's best knowledge, patient studies having recorded height, weight, injected dose, and absence of multiple metastases. Data acquisition was done under General Electric's (GE) Discovery 670DR (model name) SPECT/CT, fitted with a low energy high, resolution collimator and 3/8inch sodium iodide detector. Radiolabeling of the kit was carried out with pertechnetate obtained from a 99Mo/99mTc generator (SDS). On average, 45mCi of 99mTc was added to the lyophilized vial containing 25μg of HYNIC-PSMA-11. An average adult dose of 15-20mCi per patient was injected, and images were acquired 2-3hrs post-injection. A whole-body planar scan was acquired, followed by vertex to mid-thigh 3 bed SPECT-CT. Post-acquisition, fused images were analyzed on Xeleris 4.0 DR for understanding the biodistribution and quantifying the corresponding SUV in various soft tissue and skeletal regions. Results: High SUV values were noted in the prostate (primary lesion), kidneys, salivary glands (parotid and submandibular), liver, and spleen. The SUV values graph obtained for soft tissue clearly depicted the path of renal clearance, as is evident from the values of the kidney and bladder. Secondly, the skeletal SUVmax values of the pelvis and vertebrae were observed to be higher in comparison to other bones. Conclusion: 99mTc HYNIC-PSMA-11 can give an interpretable image, and further prospective studies with standardized protocol can help establish a correlation between PSA, Gleason's Score, and SUVmax values of prostate and its clinical utility. Biodistribution was consistent with 68Ga PSMA imaging, a standard imaging radiotracer in carcinoma prostate patients.
Onco 29: Modified DFO-mAb biomolecule and its radio-labeling with Zr-89 for immuno-PET imaging: Chemistry prospective
Anjli Shrivastav, Anshika Srivastava, Manish Dixit, Sanjay Gambhir
Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: Zirconium-89 is one of the most promising metallo-radionuclides for developing new immuno-positron emission tomography agents for in vivo imaging. It has half-life of 3.8 days (t1/2 78.41 hrs) and a multiple decay mode that involves β+ = 22.3%, electron capture = 76.6%, and Emax(β+) = 897keV, Eave(β+) = 396.9keV, Rave(β+) = 1.18mm, Eγ = 908.97keV, Iγ = 100%. Conjugating with DFO-like chelating agents to monoclonal antibodies (mAb) is a pivotal step in preparing 89Zr based for PET imaging. This conjugation process involves linking these chelators to mAbs, creating a stable complex that selectively targets specific biomarkers. Development of these radiopharmaceuticals enhances non-invasive PET imaging, offering precise insights into disease processes. Materials and Methods: All the production and purification reagents were purchased from commercial sources. Zirconium-89 (89Zr) was produced via 89Y (p, n) 89Zr nuclear reaction with proton energies in the range of 11 to 14 MeV. Solid phase purification using Hydroxamate based resin with good purity. After purification, 89Zr was used to radiolabelled the modified chelator (DFO-mAb) as per literature protocol. The final product was assessed for radiochemical purity, stability, and immunoreactivity. Results: The chemistry of modified DFO to conjugate with mAb was explored and characterized by analytical tool such as mass spectrometry, 1H and 13C NMR. These modified DFO were conjugated with mAb and further radiolabeled with 89Zr, and their QC analysis was assessed by r-TLC and HPLC, which showed excellent radiochemical purity. The radiolabeled 89Zr-DFO-mAb was performed in both in-vitro stability and in-vivo studies. The in-vivo distribution of 89Zr mAb showed standard uptake over vital organs such as spleen, liver, kidney and bladder with no trans-chelation of the activity upto 72 hr p.i. Conclusion: We have achieved a sustainable production yield of 87 ± 2% with a specific activity of 464-500 mCi/µg. The labeling efficiency of the modified DFO-mAb with Zr-89 was >99%, and the prepared radiopharmaceuticals were assessed by numerous quality assurances to quantify for clinical application. The in-vitro and in-vivo studies were also showed good result.
Onco 30: Feasibility of glomerular filtration rate and split renal function assessment using Ga-68 DOTANOC PET: Comparison with Tc-99m DTPA scintigraphy
Zahra Ambarin, Harmandeep Singh, B. R. Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: Ga-68 DOTANOC ligands are utilized for the diagnosis and treatment of neuroendocrine tumors. Their accumulation in kidneys, attributed to the presence of somatostatin receptors (SSTR) and their urinary excretory pathway, suggests a potential stand-in marker for renal function evaluation. This study aims to explore the feasibility of evaluating renal function parameters, including glomerular filtration rate (GFR) and split renal function (SRF), based on renal uptake observed in Ga-68 DOTANOC PET/CT images, in comparison with Tc-99m DTPA scintigraphy. Materials and Methods: Retrospective evaluation of Ga-68 DOTANOC PET/CT images and Tc99m-DTPA scans was performed in neuroendocrine tumor patients. PET parameters such as SUVmean, CT volume, PET MTV, and kidney counts were collected. Total kidney uptake was calculated (SUVmean × volume), and SRF was assessed. Renal function correlations were drawn between these parameters and Tc-99m DTPA results. Results: The study included ten patients. Positive correlations were observed between split renal function derived from both CT volume and MTV (p-value = 0.03; r = 0.6). GFR exhibited a significant correlation with SUVmean (p-value = 0.03; r = -0.6), while the correlation with MTV was not significant (p-value = 0.2; r = 0.3). These findings suggest that Tc-99m DTPA scintigraphy for evaluating relative renal function and radiation-induced nephrotoxicity in clinical settings may be replaced by Ga-68 DOTANOC PET, thereby saving time and lowering the number of pointless tests. Conclusion: Renal Ga-68 DOTANOC uptake demonstrates promising correlations with renal function parameters. The method employed for approximating renal parenchymal volume on PET images appears to be reliable, offering a potential alternative to traditional renal function assessments in patients with neuroendocrine tumors.
Onco 31: 68Ga-Pentixafor PET/CT based in vivo quantification of CXCR4 receptors as an imaging biomarker for assessing initial disease burden and response to chemotherapy in Multiple myeloma: Comparison with 18F-FDG PET/CT
Harneet Kaur, H. Kaur, M. Sachdeva, S. Sreedharanunni, A. Watts, P. Malhotra, R. Singh, B. Singh
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: 68Ga-Pentixafor PET/CT targets CXCR4 receptors which are known to be over-expressed in multiple myeloma (MM). The diagnostic effectiveness of 68Ga-Pentixafor PET/CT in comparison to 18F-FDG PET/CT for the initial assessment of the disease and response evaluation to various chemotherapy treatments was investigated in the present study. Materials and Methods: Thirty-one (18 males and 13 females; median age of 55 years) newly diagnosed multiple myeloma (MM) patients were enrolled prospectively. Upon presentation, their clinical information and baseline laboratory parameters were assessed. These parameters included: serum protein electrophoresis (SPEP), immunofixation assay (IFE), serum free light chain assay (SFLC) and fluorescence in situ hybridization (FISH). Additionally, we quantified the expression of CXCR4 in bone marrow (BM) aspirates and biopsy samples using flow cytometry and immunohistochemistry (IHC) analysis respectively. For treatment, patients received a combination of at least three or four drugs, including cyclophosphamide, corticosteroids (dexamethasone), immunomodulating agents (thalidomide, lenalidomide), proteasome inhibitors (bortezomib) and monoclonal antibody (Daratumumab). All patients underwent 68Ga-Pentixafor and 18F-FDG PET/CT scans both at baseline and at 6-mo after initiation of chemotherapy treatment. PET/CT data was reconstructed and SUVmax values for all the identified lesions (if there were five or fewer) or for the five most avid lesions (if there were more than five) were evaluated. These baseline and follow-up PET/CT data, along with clinical response criteria based on the International Myeloma Working Group (IMWG), were used to categorize patients into response categories. These categories were partial response (PR), very good partial response (VGPR), complete response (CR), stable disease (SD) and progressive disease (PD). Results: Serum electrophoresis revealed the characteristic M-spikes of multiple myeloma in 26 out of 31 patients, with a mean band value of 4.03 ± 2.79 g/dl, while 5 out of 31 patients had no detectable M-spike. Among the 25 patients for whom immunofixation assay results were available, the breakdown was as follows: IgG-λ (n = 7), IgG-κ (n = 9), IgA-κ (n = 3), IgA-λ (n = 2), κ-light chain (n = 3), and λ-light chain (n = 1). The κ/λ-ratio values (available for 29 patients) ranged from 0.002 to 15200. Fluorescence in situ hybridization (FISH) analysis was conducted in 19 out of 31 patients. The results categorized 12 patients as high-risk, 1 as intermediate risk, 5 as standard risk and 1 as low risk. At baseline, the mean SUVmax values derived from 68Ga-Pentixafor PET/CT were significantly higher (by a factor of 2.5) than those obtained from 18F-FDG PET (12.03 ± 9.9 versus 4.72 ± 3.54). Flow cytometry analysis assessed the intensity (MFI) and percentage of stained cells for CXCR4 receptors, with mean values of 2988 ± 3107 and 30.36 ± 28.70 (n = 21) respectively. Quantitative IHC staining provided CXCR4 intensity scores using a visual method, with a mean value of 5.23 ± 2.73 (ranging from 1.0 to 9.0) for the 30 patients assessed. The study found that among the study subjects (n = 31), 12 showed a partial response (PR), 6 showed a very good partial response (VGPR), 9 achieved a complete response (CR), 1 had stable disease (SD) and 3 patients experienced progressive disease (PD). Both 68Ga-Pentixafor and 18F-FDG PET/CT follow-up imaging at approximately 6 months showed a decrease in mean SUVmax values in patients with PR, VGPR and CR. The percent decrease in PR was more pronounced in 68Ga-Pentixafor compared to 18F-FDG PET (61.5% vs. 43.3%). Conversely, in patients with VGPR and CR, the decrease was 56.6% vs. 68.8% and 78.65% vs. 78.6%, respectively. On the other hand, in patients with PD (n = 3), the increase in mean SUVmax value on 68Ga-Pentixafor PET was significantly higher than on 18F-FDG PET (20.5% vs. 9.8%). In the case of one patient showing SD, 68Ga-Pentixafor imaging showed nearly stable baseline and follow-up SUVmax values (3.76 vs. 4.04), but 18F-FDG PET showed a lower value on follow-up imaging (6.12 vs. 3.76). The mean SUVmax values for the 31 patients on follow-up 68Ga-Pentixafor PET were significantly higher (p < 0.05) than those on 18F-FDG PET/CT (4.32 ± 4.05 vs. 1.99 ± 2.14). In the overall response assessment, both techniques performed equally well in CR and VGPR. However, in PR, follow-up 68Ga-Pentixafor PET showed a greater decrease in SUVmax than 18F-FDG. Similarly, in PD, 68Ga-Pentixafor showed a higher increase in SUVmax (20.5%) compared to 18F-FDG follow-up PET imaging. Conclusion: 68Ga-Pentixafor PET/CT was found superior (higher mean SUVmax) to 18F-FDG PET/CT both in initial disease evaluation and response assessment to chemotherapy in MM patients. Integrating patients’ disease risk factors with the CXCR4 receptors’ disease burden as assessed by 68Ga-Pentixafor, may enhance the precision of disease evaluation and response assessment in this patients’ population.
Onco 32: Radiolabelled plerixafor as a theranostic molecule for targeting CXCR4 receptor expressing cancers: A translational study
Tamanna Lakhanpal, Jaya Shuklaa, Yogesh Rathorea, Rajender Kumara, Pankaj Malhotrab, Gaurav Prakashb, Alka Khadwalb, Amanjit Balc, B. R. Mittala
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: The emerging science of nuclear medicine emphasizes the use of radionuclides tagged vector molecules that are delivered to specific targets. The vector molecules may carry radionuclides for imaging or therapeutic use. The radiolabelled vector, agonist, or antagonist may provide a landscape of disease spread and help in targeted radionuclide therapy. Chemokines favor leukocyte infiltration, promote tumor growth, angiogenesis, and metastasis. Chemokines receptor 4 (CXCR4) is over-expressed in various cancers such as lymphoma, breast cancer, etc. Plerixafor is a CXCR4 antagonist and can be radiolabelled for imaging, targeted radiation therapy, and evaluation of response to therapy. Materials and Methods: Various parameters (temp, pH, time, and reaction volume) for conjugation of Plerixafor with different bifunctional chelating agents (DTPA, NOTA) and conjugation of Plerixafor for radiolabelling with 68Ga and 177Lu for imaging and therapy were optimized. Quality control checks of radiotracers such as physical appearance and pH determination; radionuclide purity; radiochemical purity; sterility; pyrogenicity; serum stability were performed. The binding affinity and cytotoxicity studies were performed in CXCR4 expressing cancer cell lines. Physiological biodistribution studies were conducted in normal rats. Results: DTPA conjugated (1087 Da) and NOTA conjugated (1014 Da) Plerixafor determined mass spectra. Radionuclide and radiochemical purity of 68Ga and 177Lu Plerixafor was ≥ 99%. Synthesized radiotracers were stable, sterile and pyrogen-free, and suitable for intravenous administration. The radioligand binding assay confirmed high target efficacy (Kd = 57.16 nM) of 177Lu-Plerixafor towards CXCR4 expressing cancer cells. Furthermore, the log absolute IC50 concentration of 177Lu-Plerixafor in cytotoxicity studies was 2.628 nM. Nuclear receptor expression was also observed in immunocytochemistry. In-vivo physiological biodistribution of 68Ga-Plerixafor was in the liver (6.36%), spleen (11.56%), and lung (3.57%). Conclusion: In-vitro cell-lines and biodistribution studies of radiolabelled Plerixafor elicits theranostic potential for CXCR4 over-expressing cancers
Onco 33: 18 FDG PET-CT imaging in T-cell lymphomas: An institutional experience
Deepak K Jha, Dharmesh Paliwal, Renjith M. Varghese
Department of Nuclear Medicine, Command Hospital, Pune, Maharashtra, India
Introduction: T-cell lymphomas comprise a heterogeneous group of uncommon lymphomas. Approximately 10–15% of NHLs are of T-cell or natural killer (NK)-cell origin. These tumors are broadly separated into those with predominantly leukemic, extranodal, or nodal presentation. Studies in recent years have confirmed that most of these subtypes have a poorer prognosis than most B-cell NHL subtypes. There has been a widespread belief that FDG PET/CT is less useful in the assessment of T-cell lymphoma than in other types of lymphoma, on the basis of reports of low rates of FDG positivity. Hence this study was conducted to look for disease activity and patterns, if any in such patients. Materials and Methods: A retrospective review of patients with T-cell lymphomas who underwent PET/CT examination for initial disease staging or at disease relapse over a three-year period was undertaken. Disease subtypes were grouped according to World Health Organization categorization of mature natural killer cell–T-cell neoplasms. Sites of disease involvement were documented according to cutaneous or extranodal, nodal, and visceral locations. The maximum standardized uptake value (SUV) was recorded for each patient. Results: A total of 15 patients (9 males:6 females) were included who had histological diagnosis of T-cell lymphomas. Twelve (80%) out of the 15 patients showed abnormal FDG uptake in at least one site. Of those 12 patients, six (50%) had abnormal cutaneous or subcutaneous uptake, ten (83%) had FDG-avid lymphadenopathy, and five (42%) had FDG-avid extra-nodal disease other than cutaneous involvement. The Standardized uptake values (SUV)s were significantly higher in systemic anaplastic large cell lymphoma & angioimmunoblastic T-cell lymphoma than in mycosis fungoides, NK cell–T-cell lymphoma and peripheral T-cell lymphoma. Conclusion: 18 FDG PET-CT detects extra-nodal/cutaneous involvement which is a common finding in patients of T-cell lymphomas and thus helps in staging and monitoring treatment response.
Onco 34: 18F-FDG PET/CT for evaluation of post-operative Osteosarcoma patients with prosthesis in-situ
Shamim Ahmed Shamim, Naresh Kumar, Sahil Jaswal, Himanshu Kumar Gupta, Shah Alam Khan, Sameer Rastogi, G. Shivanand
Department of Nuclear Medicine, AIIMS, New Delhi, India
Introduction: Osteosarcoma is the second most frequent pediatric malignant bone tumor, frequently surgically managed with limb salvage rather than amputation. Less frequently, it occurs in adults where it represents secondary malignant degeneration of primary bone pathology. Biopsy is considered as the gold standard for the diagnosis of osteosarcoma due to its accuracy rate of 98%. Local recurrences are seen in up to 9% of osteosarcoma patients, with CT and MRI imaging often limited by metal artifacts in patients having in-situ prosthesis. Functional imaging using 18F-FDG-PET/CT can differentiate between benign and malignant lesions based on the metabolic activity, particularly in these type of patients. In addition, the acquisition of PET data is not much affected by metal implants, which frequently are present when patients have undergone limb-sparing bone resection and prosthetic bone reconstruction. Thus, present study is aimed to evaluate the diagnostic accuracy of 18F-FDG-PET/CT for detecting recurrences in prosthetic osteosarcoma patients. Materials and Methods: We retrospectively reviewed the primary osteosarcoma patients earlier treated surgically with limb salvage and/or neoadjuvant chemotherapy (NACT) from 2017 to 2020, those who undergone imaging evaluation with 18F-FDG-PET/CT for recurrence assessment and response evaluation. Patients were followed-up or undergone biopsy/surgery after PET-CT for confirmation of PET-CT findings. Results: A total of 31 patients (21 male, 10 female) of prosthetic osteosarcoma, mean age 24.22 ± 14.15 years were included in this study. Of 31 primary osteosarcoma patients, 20/31 patients underwent FDG PET/CT to look for post-treatment suspected local recurrence and metastasis and 11 patients for response evaluation to surgery/ NACT. Of 20 patients with suspected recurrence and metastasis, 3 had local recurrence, 3 had lung nodules only, 7 had local site recurrence along with lung nodules and remaining had no uptake on FDG PET/CT. Of 11 patients, 8 patients had residual diseases post-surgery/post-NACT, while 3 had no definite evidence of metabolically active lesions. The maximum standard uptake values (SUVs) were ranged from 2.6 to 16.5. Conclusion: Osteosarcoma patients with recurrences and metastasis are well visualized by FDG PET/CT, demonstrating either solid or peripheral/nodular FDG uptake with a wide range of maximum SUVs. 18F-FDG-PET/CT showed valuable results for detecting recurrence(s) in osteosarcoma patients with suspicious of relapse after treatment, particularly in the detection of local relapse and lung metastasis.
Onco 35: Role of PSMA PET-CT in detection of residual/recurrent malignant brain tumours
Mansha Vohra, Ram Singh Meena, Himanshu Bansal, Bhawani Shankar Sharma, Jitendra Solanki, Anushree Punia, Shikha Dhal, Sumit Goyal
Department of Nuclear Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, India
Introduction: PET has emerged as an additional prominent non-invasive imaging modality for CNS tumours. For detection of recurrent /residual disease, the available modalities are MRI & FDG PET-CT. There are few limitations of these modalities in detection of residual/recurrent disease in brain parenchyma post-treatment. It is vital to investigate the concept of neovascularization of the tumour tissue with help of PSMA PET-CT in detection of residual/recurrent disease. It could not differentiate the grading of tumour but it is very helpful to differentiate viable and non-viable tumour tissue after the treatment. Materials and Methods: A prospective analysis of MRI/ histopathological proven patients of brain tumours with recurrent / residual lesions (n = 30; age range 08-70 years; mean age 51.4 years; Male to female ratio 5:1) was evaluated. All the patients were treated earlier, either in combination or solely with surgery, radiotherapy or chemotherapy. The patients were referred for PSMA PET-CT on the basis of clinical and imaging suspicion of residual / recurrent disease. MRI imaging follow up was considered as gold standard for recurrent/residual diagnosis which were acquired within 10 to 15 days after or before PSMA PET-CT. In 15 patients FDG PET-CT was also performed in order to compare the universal tracer with PSMA PET-CT. Results: Thirty patients who underwent PSMA PET-CT investigation for post-treatment monitoring were diagnosed as primary brain or spinal cord tumors. On region based disease analysis, 26 patients had cortical parenchymal lesions, whereas remaining 4 had a lesion in the brain stem. Out of 30 patients, PSMA PET-CT and MRI were concordant in 27 patients (90%) for presence and absence of disease. On clinical follow-up of 12 months of the patient who were negative for PSMA PET-CT but positive for MRI, there was no progressive deterioration in signs and symptoms and the follow-up MRI scans showed no significant interval change. In 15 patients, where comparative study of PSMA PET-CT and FDG PET-CT was conducted, PSMA PET-CT was more accurately positive than FDG PET-CT. This may be due to higher physiological uptake of FDG in brain and PSMA has near about no uptake. Conclusions: This study concluded that PSMA PET-CT has higher diagnostic accuracy as compared to conventional imaging for detection of suspected residual / recurrent disease in malignant brain lesion patients and also useful in searching the theragnostic applications.
Onco 36: Utility of F18 FDG PET CT scan in further surgical management of locally advance head and neck squamous cell carcinoma patients in definitive chemo-radiation setting
T Kalawat, L. C. N. D. Praveen, R. G. Manthri, H. Narendra, B. Vijaylakshmi Devi, A. K. Chowhan, D. Bhargavi, S. Jilla
Department of Nuclear Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
Introduction: Among patients with locally advance head and neck squamous cell cancer post chemoradiotherapy, surgical clearance of neck nodes is being performed as standard of care after considering CECT head and neck scan findings. The current study reformed to compare the results of CECT Vs F18 FDG PET CT to find out the treatment responders and non-responders before deciding further surgical clearance of neck nodes. Materials and Methods: In this prospective study, the non-inferiority of F18 FDG PET CT guided surveillance using Hopkins criteria performed 10-14 weeks after the end of chemo-radiotherapy, with neck dissection performed only if PET CT positive. The primary end point of the study planned, is to avoid surgical management if F18 FDG CT findings shows no significant FDG avid nodes. Results: Total n = 24 patients were evaluated using F18 FDG PET CT Hopkins interpretation criteria compared with CECT for post treatment response. CECT is positive for residual disease in 14 patients and using Hopkins criteria 8 patients were positive. Total 20/24 patients avoided from undergoing surgery using PET CT (includes 16 patients negative for residual disease and 4 patients with metastasis). Conclusion: F18 FDG PET CT metabolic imaging with Hopkins criteria in post chemoradiotherapy head and neck cancer patients are highly useful and superior than CECT in segregating the responders and non-responders’ patients. F18FDG PET CT helps the clinician to take the further management decision which may or may not require surgical excision for cure of disease at the primary site.
Onco 37: Role of 18F FDG PET-CT in radiogenomics of carcinoma breast
Alok Mandal, Deepanksha Datta, Rajesh Kumar, Sameer Taywade
Department of Nuclear Medicine, AIIMS, Jodhpur, Rajasthan, India
Introduction: Radiogenomics identifies associations between imaging phenotypes (“radio”) and tumor genome (“genomics”). Breast cancer is the most common malignancy among women worldwide. It shows different relapse rates, prognosis and therapy response features according to different molecular phenotypes. In this study, we evaluated the relationship between metabolic activity of primary tumour and different molecular phenotypes of breast cancer. Materials and Methods: It is a retrospective study conducted in nuclear medicine department, AIIMS Jodhpur. Inclusion criteria was HPE proven breast carcinoma patients who had undergone 18F FDG PET-CT imaging for staging during the time period between January 2022 to December 2022 and who had Ki67 value on their HPE reports. Patients were divided into three groups on the basis of Ki67 level (High =>50%, Medium = 21-50%, Low =<20%) and divided into five molecular subgroups (Luminal A, Luminal B, Luminal B like, Her 2 enriched and Triple negative) on the basis of hormone receptor status. Metabolic parameter was obtained by calculating the ratio (SUR) of SUVmax of the primary lesion and SUVmax of liver. We compared this SUR between different molecular subgroups using ANNOVA test. Results: Total 44 patients [median (range) age = 51 (27-85) years] met the inclusion criteria. 15/44 patients were in the low ki67 group, 12/44 patients in medium ki67 group and 17/44 patients in the high ki67 group. Significant difference was found in SUR between these three groups (p value 0.037). The median SUR was highest in the high ki67 group {4.77 (1.15-9.5)} and lowest in low ki67 group {3.19 (0.79-7.39)}. Molecular subgroup was not available for 6 patients due to unavailability of complete HPE reports. Among the molecular subgroups, 11/38 patients were in the luminal B, 8/38 patients in luminal B like, 8/38 patients in triple negative, 7/38 patients in Her2 enriched and 4/38 patients in luminal A subgroup. No significant difference was found in SUR between these five groups (p value 0.386). The median SUR was highest in the triple negative subgroup {5.095 (3.06-7.39)}and lowest in the luminal A subgroup {2.525 (0.79-3.53)}. Conclusion: The metabolic ratio of primary tumor to the liver can served as a prognostic marker in detecting the aggressiveness of the tumor. Higher the SUR, the higher is the Ki 67 index. Though no significant difference was found in the SUR between the molecular subgroups, triple negative breast cancer showed relatively higher SUR, and luminal A subgroup showed lowest SUR value. Future prospective studies are warranted to establish this finding.
Onco 38: Utility of 18F-FDG PET-CT in the staging of patients with Langerhans cell histiocytosis
Priyank Rajput, Deepanksha Datta, Rajesh Kumar, Sameer Taywade
Department of Nuclear Medicine, AIIMS, Jodhpur, Rajasthan, India
Introduction: Langerhans cell histiocytosis (LCH) is a rare disease characterized by the clonal proliferation of abnormal Langerhans cells (antigen-presenting immune cells). LCH can affect children and adults with wide range of clinical manifestations. LCH is classified according to sites of involvement into single system and multisystem disease. It is important to distinguish between the two types of LCHs because of different therapeutic regimens and prognoses. Accurate staging is essential for selecting the most appropriate therapy that range from local surgery to chemotherapy. Materials and Methods: It is a retrospective study done in the Department of Nuclear Medicine, AIIMS Jodhpur. The inclusion criteria was patients diagnosed with LCH on biopsy. The involvement of LCH in each system was assessed by a 18F-FDG PET/CT scan. The parameters taken in the study were the organ involved and median SUVmax of the lesions. Results: 18F-FDG PET/CT of 7 patients (Median age = 2years, Range = 10 months-39 years) diagnosed with LCH on biopsy. 6/7 patients were pediatric (under 4 years) and 1 patient was adult. 6/7 patients were male and only one patient was female. All the7 patients presented with multiple system involvement. There was no case of isolated disease. 5/7 patients had involvement of skeletal system (Median lesional SUVmax- 4.9). Out of which most common involved bone was skull bone. 5/7 patients had lymph nodes involvement (Median lesionalSUVmax-2.5). 3/7 patients had liver involvement (Median lesionalSUVmax-2.3). 3/7 patients had lung involvement. 3/7 patients had cutaneous involvement (Median lesionalSUVmax-2.7). Brain was involved in 2/7 patients (brainstem and right cerebellar hemisphere, hypothalamic region (SUVmax-24.2) and bilateral cerebellum (right SUVmax- 30.8) in one patient and meningeal, bilateral choroid plexuses (SUVmax-22) & pituitary (SUVmax-6.4) involvement in second patient). Conclusion: 18F-FDG PET/CT is useful for evaluating the extent of disease at the initial stages of diagnosis and this aiding in risk stratification.
Onco 39: Impact of additional FDG PET information on ct-only radiotherapy planning of esophageal cancers
Nitish Chavan, Rajesh Kumar, Sameer K. Taywade, Deepanksha Datta
Department of Nuclear Medicine, AIIMS, Jodhpur, Rajasthan, India
Introduction: Radiotherapy plays an important role in the definitive and palliative treatment of esophageal cancers. For radiotherapy (RT) planning in esophageal cancers, 3D-CT is the most commonly used modality. Tumour volume delineation based on CT-alone is challenging because one has to rely only on the morphologic changes. In recent times, the use PET for RT planning has gained much interest and greatly improves tumour volume delineation. Our aim was to demonstrate the incremental value of 18F-FDG PET/CT over conventional CT in determination of tumour volumes. Materials and Methods: This is a prospective study done at Department of Nuclear medicine, AIIMS Jodhpur, which included patients with biopsy proven esophageal cancer who underwent baseline 18F-FDG PET/CT using standard procedure. 3D-CT and 3D-PET/CT were used to calculate tumour volumes. Gross tumour volume (GTV) was the visible tumour mass on hybrid as well as anatomical imaging, clinical tumour volume (CTV) was obtained by taking a margin of 4 cm cranio-caudally & 1 cm circumferentially to GTV with manual removal of bone, heart, great vessels, etc. Planning tumour volume (PTV) was obtained by taking a margin of 0.5 cm in all directions to CTV. The mean tumour volumes were calculated for both 3D-CT & 3D-PET/CT and compared using Student's t-test. Results: 42 patients met the inclusion criteria and their mean age was 56.8 ± 11.7 years with Male:Female = 20:22. The mean GTV, CTV and PTV on 3D-CT were 34.5 ± 23.1cc, 196 ± 87.8cc and 349 ± 129cc, and on 3D-PET/CT were 29.2 ± 19.0cc, 175 ± 88.3cc and 313 ± 129cc respectively. The addition of PET to 3D-CT changed the tumour volumes in all 42 patients, 32/42 showed a decrease (average decrease 24.7%, mean 8.52 ± 12.7cc) while 10/42 (average increase 21.8%, mean 5.06 ± 4.22cc) showed an increase in the tumour volumes on 3D PET/CT over 3D-CT. There was significant mean difference for GTV, CTV and PTV between 3D-CT and 3D-PET/CT were 5.28 ± 1.95cc (p = 0.01), 21.30 ± 5.54cc (p < 0.001) and 35.3 ± 8.95cc (p < 0.001) respectively. Conclusion: The addition of PET resulted in both increase and decrease in the tumour volumes being delineated on CT-alone. This may have significant impact on patient outcomes, as successful treatment of esophageal cancer patients relies greatly on precise delivery of radiation therapy. Moreover, there maybe modifications in the radiation dose being delivered to adjacent organs thus resulting in lesser toxicity. Thus, addition of PET/CT provides incremental value in RT planning of esophageal cancers as compared to CT-alone.
Onco 40: Comparison of 18F-FDG PET/CT and CECT in detecting residual disease in locally advanced head and neck squamous cell carcinoma managed with primary chemo-radiation therapy
Shamim Ahmed Shamim, Naresh Kumar, Roma, Himanshu Kumar Gupta, Sahil Jaswal, Atul Sharma, Raja Pramanik, Mukesh Yadav, Suman Bhaskar, Ahitagni Biswas, Rajeev Kumar, Aanchal Kakkar
Department of Nuclear Medicine, AIIMS, New Delhi, India
Introduction: There is no clear and established guidelines as of now for follow-up imaging strategies in monitoring of Head & Neck Squamous Cell Carcinoma (HNSCC) after completion of chemo-radiation for evaluation of patients with residual or recurrent disease. Keeping this in view, we conducted this prospective study to compare the role of diagnostic CECT head & neck and whole body 18F-FDG PET-CT scan in detection of residual disease in locally advanced HNSC. Materials and Methods: Histologically proven locally advanced HNSCC patients who were planned for definitive chemo-radiotherapy as first line treatment with curative intent were recruited from head and neck cancer OPD. As a routine policy, a pre-therapy baseline FDG PET/CT and CECT were performed in all patients within a time frame of one week. After baseline imaging was obtained, the patients underwent follow-up PET-CT and CECT scan for response evaluation after 10-12 weeks of completion of chemo-radiotherapy regimen. All scans were independently evaluated by two experienced Nuclear Medicine physicians & radiologists and were reported jointly. Results: A total of 72 patients (67 men; 5 women), mean age 56.5 ± 11.3 years of locally advanced HNSCC were included in this prospective study, who underwent baseline diagnostic CECT head & neck and whole body 18F- FDG PET-CT. Of 72 patients at baseline CECT and FDG PET/CT, 28 patients had concordance while 44 patients had discordance between CECT and FDG PET-CT imaging. The follow-up was available/completed in 50 patients only, and rest of 22 patient either lost to follow-up or died during the course of treatment. Of 50 follow-up patients, both the modalities showed concordant results for complete response in 10 patients, and for residual disease in 31 patients. Thirty one (31) patients with residual disease on both modalities, underwent FNAC/ biopsy correlation. Out of these 31 patients, 2 patients were negative for residual disease at primary and lymph node site and remaining 29 patients showed positive results for residual disease at primary and/ or lymph node site. Another 9 patients with discordant results on both modalities, who showed residual disease on CECT and complete metabolic response on FDG PET/CT were kept on further clinical follow-up and there was no evidence of recurrence till end of the study and all were alive till the end of the study. FDG PET-CT showed higher specificity (90.4% versus 52.6%) and PPV (93.5 versus 77.5%) for residual disease detection in these patients, though the sensitivity and NPV were comparable in both the modalities. Conclusion: 18F-FDG PET-CT is a better predictor for true positive and true negative cases of residual disease, and a better modality to evaluate distant metastases compared to CECT head & neck.
Onco 41: Role of baseline 18F-PSMA-1007 PET/CT derived semi-quantitative and volumetric parameters in intermediate and high-risk prostate cancer
K. R. Chandekar, S. Satapathy, H. Singh1, R. Kumar1, N. Kakkar1, S. Kumar1, S. K. Singh1, B. R. Mittal1
Department of Nuclear Medicine, AIIMS, New Delhi, 1Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: Imaging of prostate cancer (PCa) has been revolutionized by widespread clinical adoption of PET tracers targeting the prostate specific membrane antigen (PSMA). The utility of 68Ga-PSMA PET-derived semi-quantitative parameters has been demonstrated by several studies. Owing to dearth of similar literature with the novel radiotracer, 18F-PSMA-1007, we aimed to explore the utility of baseline 18F-PSMA-1007 PET/CT derived semi-quantitative and volumetric parameters in predicting initial risk-stratification category and presence of metastases in PCa patients. Materials and Methods: Treatment-naïve patients with biopsy-proven, NCCN-defined intermediate or high-risk PCa were prospectively recruited. Each patient underwent 18F-PSMA-1007 PET/CT for initial staging. SUVmax and SUVmean of the primary tumor were obtained using appropriate volumes of interest (VOIs) over the dominant intra-prostatic lesion. Volumetric parameters such as prostate PSMA-tumor volume (PSMA-TVp) (in cm3) and prostate total lesion PSMA (TL-PSMAp) (in g/ml x cm3) were derived using the automated threshold method (40% of SUVmax) with manually adjusted VOIs to exclude tracer uptake of surrounding normal tissues (bladder/rectum). Group differences were evaluated using the Mann–Whitney U test (for continuous variables) and Chi-square test (for categorical variables). Spearman's correlation was performed to assess the correlation between the above parameters with serum prostate-specific antigen (PSA) levels and Gleason score (GS). Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for PSMA-TVp and TL-PSMAp to identify high-risk PCa. Results: The study population comprised of forty PCa patients (8 – intermediate-risk and 32 – high-risk) with a mean age of 68.0 ± 8.6 years. Mean serum PSA levels were 50.2 ± 41.6 ng/mL (range, 7.6–169). Median biopsy GS was 4+3 (grade group 3). Intra-prostatic lesions were detected in all patients. Regional nodal metastases were detected in 23/40 (57.5%) patients, extra-regional nodal metastases in 17/40 (42.5%), skeletal metastases in 16/40 (40%) and visceral metastases in 3/40 (7.5%) patients. The median primary tumor SUVmax and SUVmean values were not significantly different between the intermediate-risk and high-risk groups. However, the median PSMA-TVp (10.76 vs 2.95) and TL-PSMAp (118.1 vs 28.45) were significantly higher in the high-risk group compared to the intermediate-risk group (both p-values ≤ 0.005). ROC curve analysis revealed that PSMA-TVp and TL-PSMAp could be used to effectively differentiate high-risk PCa from intermediate-risk PCa (AUCs 0.813 and 0.891, respectively; both p values < 0.001) with optimal cut-off values of 5.76 and 71.7, respectively. PSMA-TVp and TL-PSMAp showed moderate significant correlation with GS (r = 0.584 and 0.477, respectively; both p values ≤ 0.002). TL-PSMAp showed moderate significant correlation with serum PSA level (r = 0.462, p = 0.003). TL-PSMAp ≥ 71.7 was associated with more frequent regional and extra-regional nodal metastases (both p values < 0.05). However, none of the volumetric parameters were predictive of skeletal and visceral metastases. Conclusion: 18F-PSMA-1007 PET/CT based primary tumor volumetric parameters have a potential role in predicting initial-risk stratification category and presence of nodal metastases in treatment-naïve PCa patients.
Onco 42: Reinforcing the inefficacious outcome of non-evidence based solid cancer management with the aid of FDG PET-CT
P. A. Meivel, R. Narmadha, R. Arulmurugan, M. Rumesh Chandar, Aswin Chandran, K. Bharadhwaj, K. S. Rajkumar
Department of Nuclear Medicine, PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India
Introduction: Non-evidence based therapy in the form of ayurveda, siddha, unani, homeopathy etc is sought after due to the relative affordability and accessibility compared to evidence based management while cultural factor also plays a significant role. We aim to reiterate the poor outcome of non-evidence based management in solid tumors with the help of FDG PET on recurrence, restaging, and response assessment. Materials and Methods: Retrospective observational study of patients who underwent FDG PET-CT following non-evidence based treatment for solid malignancies irrespective of prior evidence based treatment. FDG PET-CT was performed according to the recommended guidelines in the department of Nuclear Medicine in a tertiary care hospital. Overall, a total of 35 patients with history of non-evidence based treatment for solid malignancy had FDG PET-CT between March 2022 and September 2023. Comparison of previous cross-sectional imaging wherever available was done according to RECIST and PERCIST criteria. Results: Out of the 35 patients, 16 were females and 19 were males with median age of 58 years (range 11 - 85 years). The organ wise distribution was breast (12), colorectal (7), esophagus (4), stomach (2), prostate (2), hypopharynx (2), sarcoma (2), one each of ovary, lung, periampullary and melanoma. Fifteen patients had received evidence-based treatment in the form of chemotherapy, radiotherapy, and surgery; out of which four patients had completed the protocol treatment before going for non-evidence based treatment. The median duration of non-evidence based treatment was 8 months (range 2-24months). 14 patients had prior PET-CT for optimal comparison, 5 patients had prior CT and 16 patients did not have any previous cross-sectional imaging. Almost all the patients had progressive or recurrent disease found on FDG PET-CT. All the 14 patients who had baseline or prior to non-evidence based treatment were found to have disease progression depicting 100% inefficacy. On review, we found 21 patients are undergoing evidence- based treatment and doing well except one had disease progression despite receiving chemotherapy. Seven patients are continuing with the native treatment, four patients succumbed to the disease and three patients could not be followed up. Conclusion: Our study reinforces the futile outcome of non-evidence based treatment in the management of solid tumors. The department of Nuclear Medicine can be a pivot to guide and counsel the patients for accessible and affordable evidence-based oncological treatment as a standard of care. In our study, almost all the patients could have had better treatment outcome with evidence-based management. Fortunately, around 60% of the patients from our study continued further management in the form of evidence-based treatment and are doing better on follow up.
Onco 43: Reproducibility of semiquantitative and volumetric PET/CT parameters in carcinoma lung patients
Anshul Arora, Priyavrat Purohit, Piyush Aggarwal, Harmandeep Singh, Rajendrer Kumar Basher, B. R. Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: SUV is the semiquantitative parameter for measurements in PET/CT. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are measures of global tumor burden and can have prognostic value in different malignancies. Manual and automated approaches of lesion segmentation have been developed for tumor quantification on PET/CT. We aim to assess the inter- and intra-observer reproducibility of PET/ CT quantitative parameters in carcinoma lung patients. Materials and Methods: Retrospective analysis of 18F-FDG PET/CT studies of patients with histopathologically confirmed carcinoma lung was done. Quantitative parameters -SUVmax, SUVpeak, SUV mean, MTV, TLG were calculated. VOI was drawn over the primary cancer for volumetric assessment with isocontouring set at 40% threshold. These measurements were done twice by one observer at different times to assess intra-observer reproducibility and once by second observer to assess inter-observer reproducibility. Wilcoxan signed rank test was used to compare median intra and inter-observer readings. Cohen's kappa test was used for agreement. Results: Thirty patients with primary lung cancer who underwent 18F-FDG PET/ CT for staging were included. A significant difference in median SUVmean was noted for intra-observer readings (8.2 vs 7.81, (p = 0.046). There was no significant difference between the rest of the PET quantitative parameters for intra- and inter-observer readings [Table 1]. There was near perfect agreement between intra and inter-observer readings of SUVmax and SUVpeak. There was a moderate agreement between intra-observer readings of SUVmean, MTV and TLG. However, only a fair agreement was noted for inter-observer readings of SUVmean, MTV and TLG. Conclusion: The SUVmax and SUVmean show high intra and inter-observer reproducibility and near-perfect agreement, while there is higher intra and inter-observer variability for SUVmean, MTV and TLG. More reproducible and objective methods for SUVmean and PET volumetric estimation need to be explored.
| PET parameters | Intraobserver readings | Interobserver readings | ||
|---|---|---|---|---|
| Median (P) | Kappa agreement (95% CI) | Median (P) | Kappa agreement (95% CI) | |
| SUVmax | 14.2 versus 13.5 (0.18) | 0.931 (1–0.837) | 14.2 versus 14.2 (0.68) | 0.822 (0.97–0.694) |
| SUVmean | 8.2 versus 7.81 (0.046) | 0.492 (0.312–0.672) | 8.2 versus 8.13 (0.24) | 0.392 (0.566–0.218) |
| SUVpeak | 11.2 versus 10.4 (0.65) | 0.931 (1–0.87) | 11.2 versus 11.2 (0.46) | 0.863 (0.989–0.737) |
| MTV | 33.1 versus 31.7 (0.07) | 0.492 (0.312–0.672) | 33.1 versus 33.3 (0.96) | 0.359 (0.529–0.189) |
| TLG | 285 versus 248 (0.19) | 0.458 (0.636–0.280) | 285 versus 287 (0.87) | 0.359 (0.529–0.189) |
CI: Confidence interval, MTV: Metabolic tumor volume, TLG: Total lesion glycolysis, SUV: Standardized uptake value, PET: Positron emission tomography
Onco 44: Clinical impact of 18F-FDOPA PET-CT in differentiating recurrence from post-treatment changes in high grade glioma (WHO grade III and IV glioma)
Sukriti Patra, S. Patra, I. Dev, V. Rangarajan N. Purandare, A. Agrawal, S. Shah, S. Choudhury, S. Ghosh, A. D. Puranik
Department of Nuclear Medicine, Tata Memorial Hospital, Mumbai, Maharashtra, India
Introduction: High grade gliomas are the most common intracranial neoplasms associated with poor prognosis due to their inherent aggressive nature and infiltrative component. Multiparametric MRI remains the investigation of choice in the management of high-grade glioma as it has high spatial resolution and better soft tissue characterization. However, its specificity to identify early recurrence drops down significantly in post treatment settings due to permanent breach in the blood brain barrier. Hence there is always a scope for a new imaging modality to pitch in. Amino acid PET tracers, like Methionine (MET), FET and FDOPA, have been used as a problem-solving tool in such scenarios. These tracers are transported via the L-amino acid transporter type 1 (LAT1) system which are overexpressed in high grade glial tumor and demonstrate high uptake in tumor cells and relatively low uptake in normal brain parenchyma. Various studies have documented the role of F18- FET and C11-MET PET-CT. Commercial availability and the need of an on-site cyclotron limits the use of these amino acid tracers. FDOPA is easily available F18 labeled radiopharmaceutical with similar mechanism of localization through LAT1 transporters. However, very few studies have evaluated the incremental value of quantitative parameters of FDOPA PET-CT. Hence, we aimed at evaluating diagnostic value of FDOPA PET-CT in patients with high grade gliomas with equivocal findings on MR imaging or clinico-radiological mismatch. Materials and Methods: In this retrospective observational study, 63 patients of post treatment high grade gliomas who presented with equivocal features on follow-up MRI scans and referred for 18F-FDOPA PET-CT were analysed. Patients were injected 5-6mCi (185-222MBq) of 18F- FDOPA radiotracer intravenously. Regional static brain PET scan with high mA CT was acquired 20 minutes post injection. Visual score was used as qualitative parameter (score 0: No uptake, score 1: Background < lesion< striatum, score 2: Uptake = striatum, score 3: Uptake> striatum) and Tumor to contralateral striatal ratio (T-S ratio) was used as semi-quantitative parameter. It is the ratio of SUVmax of the tumor and SUVmean of contralateral striatum. Imaging findings were confirmed with histopathological report or clinical follow-up. Results: Out of 63 patients, 41 were reported as recurrent/progressive disease (based on visual score of 2 and 3); 31 of them were confirmed as recurrent/progressive disease on either histopathology/follow-up MRI scan discussed on multidisciplinary tumor board. Remaining 10 patients were interpreted as false positive. 22 patients were reported as post treatment changes (visual score: 1), only 18 of them were confirmed as post-treatment changes on either histopathology/follow-up MRI scan discussed on multidisciplinary tumor board. Remaining 4 patients were interpreted as false negative. A cut-off of 2.055 was derived based on Receiver operating characteristics curve (ROC) analysis with sensitivity of 87.8 % & specificity of 90.1 %. Conclusion: FDOPA PET-CT based parameters i.e, visual score and Tumor to striatal ratio can reliably differentiate tumor recurrence from post treatment changes in patients of high grade glioma.
Onco 45: FDG PET/CT versus bone marrow biopsy in the initial evaluation of bone marrow involvement in lymphoma patients
Ralph Emerson. P, Kanhaiyalal Agrawal, Girish Kumar Parida, Sai Sradha Patro, Parneet Singh, Tejasvini Singhal, Ashutosh Panigrahi
Department of Nuclear Medicine, AIIMS, Bhubaneshwar, Odisha, India
Introduction: Assessing bone marrow (BM) involvement is crucial in staging and managing lymphoma. Bone marrow aspiration/biopsy (BMA/BMB) is routinely employed for identifying BM involvement but is invasive and assesses limited sampling sites (usually posterior iliac crest). 18F-FDG PET/CT offers non-invasive whole-body evaluation, which is particularly advantageous in the heterogeneous involvement of BM, which may go undetected on single-site BMB. This study compares BMB with 18F-FDG PET/CT to detect BM infiltration in lymphoma and evaluates the possibility of 18F-FDG PET/CT as the standard for BM evaluation and obviating the routine use of BMB. Materials and Methods: This retrospective study included 44 patients with an established diagnosis of lymphoma - both Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). All patients underwent BMA, BMB and 18F-FDG PET/CT as a part of initial disease staging (within 4 weeks of each other). BM infiltration was considered in cases with positive BMB, or in those with a negative BMB with one or more of the following: local biopsy results corroborating with findings noted on 18F-FDG PET/CT, regression or progression of lesions on 18F-FDG PET/CT imaging obtained following chemotherapy, and morphologic CT changes suggestive of BM involvement not explained by benign findings. Results: Forty-four lymphoma patients (17 HL and 27 NHL) were included in the study. Of these, 13 were females, and the median age was 38 years (range 4-73). Twenty-one patients were positive for BM involvement as per the aforementioned criteria. Of these 21 patients, PET/CT detected 16 patients (9 HL and 7 NHL), BMB detected 11 patients (5 HL and 6 NHL) while BMA detected only 6 patients 2 HL and 4 NHL) with BM involvement. PET/CT showed a higher sensitivity (76.2%) than BMB (52.3%) and BMA (28.6%) in detecting BM involvement in lymphoma. 18F-FDG PET/CT detected BM involvement in 10 (22.7%) of those cases that were missed on BMB, and thus upstaged and changed the management. BMB detected BM involvement in 5 patients [4 NHL, 1 HL] (11.4%) missed on PET/CT, out of which 4 had diffuse FDG uptake and remaining one patient had low grade lymphoma. Conclusion: 18F-FDG PET/CT demonstrates higher sensitivity and NPV in the detection of bone-marrow involvement in lymphoma compared to BMB. Thus, 18F-FDG PET/CT can potentially replace the need for routine and invasive BMB in cases of HL and NHL, particularly in patients with multifocal tracer uptake. Moreover, PET/CT can serve as valuable tool for guiding the selection of biopsy sites with iliac crest BMB being reserved for cases with diffuse FDG uptake to differentiate malignant involvement and reactive hyperplasia. The limitation of this study was limited sample size with inclusion of both HL and NHL patients. Thus, larger prospective trials are required to assess the utility of 18F-FDG PET to determine BM involvement.


| Sensitivity (%) | NPV (%) | |
|---|---|---|
| BMA | 28.6 | 60.5 |
| BMB | 52.3 | 69.7 |
| 18F-FDG PET/CT | 76.2 | 82.1 |
NPV: Negative predictive value, BMA: Bone marrow aspiration, BMB: Bone marrow biopsy, FDG: Fluorodeoxyglucose, PET: Positron emission tomography, CT: Computed tomography
| Metastatic Lesions | |||||
|---|---|---|---|---|---|
| Primary Carcinoma | Skull (Mean ± SD) |
Vertebrae (Mean ± SD) |
Thoracic (Mean ± SD) |
Flat Bones (Mean ± SD) |
Pelvis (Mean ± SD) |
| Breast | 0.18 ± 0-45 | 0.74 ± 137 | 0.44 ± 1.25 | 0.10 ± 0.31 | 0.36 ± 0.90 |
| Lung | 0.36 ± 0.63 | 1.21 ± 1.48 | 0.79 ± 0.89 | 0.29 ± 0.47 | 0.57 ± 0.85 |
| Prostate | 1.21 ± 2.86 | 3.14 ± 3.98 | 3.71 ± 4.53 | 0.71 ± 1.14 | 2.43 ± 2.74 |
| Cervix | 0.00 ± 0.00 | 1.00 ± 1.00 | 0.00 ± 0.00 | 1.67 ± 2.08 | 1.33 ± 1.53 |
| Thyroid | 0.00 ± 0.00 | 2.33 ± 321 | 0.00 ± 0.00 | 0.33 ± 0.58 | 0.00 ± 0.00 |
Onco 46: Distribution of skeletal metastasis in malignant bone tumors – Scintigraphy and whole body SPECT/CT evaluation
K. Vidhya, Shranav Jha, L. S. Sanjith, Nikhil Kumar Gupta, Vandana K. Dhingra
Department of Nuclear Medicine, AIIMS, Rishikesh, Uttarakhand, India
Introduction: Bone metastasis is the third most frequent site of metastatic disease, with only the liver and lungs having a higher prevalence. Early diagnosis of bone metastasis can assist in preventing the complications, and is fundamental for precise distant staging and optimal management. Exploration of the distribution of metastatic lesion may aid in evaluating the primary tumor in patients with cancers of unknown primaries. Bone scintigraphy is a widely employed and standard initial imaging technique for the diagnosis of bone metastasis in malignant tumors. Various studies have suggested additional diagnostic benefit of a Whole body/trunk SPECT/CT in skeletal metastases evaluation. Methods: A total of 86 histologically proven carcinoma patients who underwent planar bone scan (PBS) and a whole-body (three-field) SPECT/CT scan from the base of the skull to the upper part of the thigh bone were included in this study. Classification of each lesion and each patient was done into three categories: “nonmetastatic,” “equivocal,” or “metastatic,” by two experienced nuclear medicine physician. The results with subsequent imaging or clinical follow-up, served as the reference standard. Results: The study included patients with an average age of 54.51 ± 12.94 years with breast, prostate and lung cancers as the most common primary cancer types. In terms of lesion analysis, a total of 796 and 519 lesions were examined using PBS and whole-body SPECT/CT, respectively. For PBS, the number of metastatic, equivocal, and benign lesions were 356 (44.7%), 62 (7.8%), and 378 (47.5%), respectively. Whole-body SPECT/CT showed 400 (77.1%) metastatic lesions, 13 (2.5%) equivocal lesions, and 106 (20.4%) benign lesions. In the per-patient analysis, bone metastasis was confirmed in 54 out of 86 patients, accounting for 62.8% of the total.
Breast Cancer mainly metastasised to vertebrae and thoracic region, indicating a preference for axial involvement
Lung and Prostate Cancer primarily affected the thoracic region, followed by the vertebrae
Cervical Cancer was associated with flat bone lesions, highlighting its distinct metastatic behavior
Thyroid Cancer metastasis mainly vertebral
Renal Carcinoma showed no significant preference for any specific site of metastasis
Lymphomas, multiple myeloma, and bladder carcinoma commonly involved vertebral sites.
| Variable | Overall: Metastatic Lesions | Wilcoxon Test | ||||
|---|---|---|---|---|---|---|
| Mean (SD) | Median (IQR) | Range | V | P Value | ||
| Whole Body SPECT/CT | 4.48(7.21) | 1.00 (5.00) | 0.00-34.00 | 678.5 | 0.927 | |
| Planar Whole| Body Bone Scan | 4.33 (6.98) | 2.00 (5.00) | 0.00-44.00 | |||
| Absolute Difference | -0.15 (3.24) | 0.00 (2.00) | -15.00-10.00 | |||
| Percent Difference | -9.2% (83.8) | 0.0% (64.3) | -100%-400% | |||
Conclusion: Our study and results found show that Whole-body SPECT/CT combined shows higher differentiation between metastatic versus non metastatic lesions and significant reduction in reporting of equivocal lesions as compared to only PBS. Bones of axial skeleton are more likely to have bone metastasis than appendicular skeleton likely attributed to active hematopoietic (red) marrow, while the appendicular skeleton contains relatively avascular fatty (yellow) marrow. It is important for both radiologists and nuclear medicine physicians to know the pattern of distribution of metastatic skeletal deposits in various cancers as it helps to characterize the nature of lesions within the skeleton. Also, this helps in expecting the sites of possible skeletal related events and its early management.
Onco 47: Differentiation of benign versus malignant pleural effusion on 18 F FDG PET-CT
Parneet Singh, Girish Kumar Parida, Tejasvini Singhal, Sai Sradha Patro, Sourin Bhuniya, Kanhaiyalal Agrawal
Department of Nuclear Medicine, AIIMS, Bhubaneswar, Odisha, India
Introduction: Pleural effusion (PE) is described as an excess of fluid in the pleural cavity. PE is common in cancer patients. PE can be reactive, secondary to some benign pathology or malignant. It is essential to distinguish malignant pleural effusion from benign causes of effusion as malignant PE signifies an advanced stage of cancer and thus, its presence can shift the intent of management from local treatment to systemic therapies. PE is conventionally characterized by pleural fluid cytology with or without immunocytochemistry which is an invasive procedure. We hereby tried to retrospectively distinguish benign from malignant PE based on its imaging characteristics on 18-F FDG PET-CT scan. Materials and Methods: This was a retrospective study including all patients with malignant pathology and pleural effusion who underwent pleural fluid cytology and 18-F FDG PET-CT study within 1 month of each other. The imaging characteristics like pleural fluid SUVmax, pleural fluid HU, SUVmax pleura and pleural thickness were evaluated. Student's t-test was used to evaluate the statistical significance of the difference of means of these imaging characteristics. ROC curve was drawn to determine the cut-off of these parameters to differentiate the two groups. Results: A total of 62 patients with PE (24 malignant and 38 benign) with a median age of 52 years (range 15-90 years) were included in the study. Of these, 28 patients had non-small cell carcinoma of the lung, 10 had lymphoma (2 Hodgkins & 8 non-Hodgkin's lymphoma), 7 had breast carcinoma, 5 had metastatic carcinoma of unknown primary, 5 had Gi malignancy, 2 had gynaecological malignancy, 2 had soft tissue sarcoma, one had neuroendocrine tumor, one had oral cancer and one patient presented with malignant pleural effusion with undefined primary. The mean, mean difference and the significance of difference of means of imaging characteristics evaluated are given in Table 1. Cut-off values of different imaging parameters with their respective sensitivities and specificities for differentiation of benign vs malignant pleural effusion are given in Table 2. Conclusion: Imaging characteristics on !8-F FDG PET-CT i.e. pleural fluid SUVmax, SUVmax pleura and pleural thickness can efficiently differentiate malignant from benign causes of pleural effusion. However, larger prospective studies are warranted to establish the broader applicability of 18-F FDG PET-Ct imaging parameters in clinical practice.
| Imaging characteristics | Mean in malignant group (n=24) | Mean in benign group (n=38) | Mean difference | Significance (P) |
|---|---|---|---|---|
| SUVmax pleural fluid | 1.7208±0.94762 | 0.9724±0.53848 | −0.74846 | 0.026 |
| HU pleural; fluid | 16.600±4.5630 | 15.311±4.1100 | −1.2895 | 0.450 |
| SUVmax pleura | 5.4712±4.03290 | 3.1368±3.56608 | −2.33441 | 0.165 |
| Pleural thickness | 6.79±4.374 | 4.21±5.458 | −2.581 | 0.798 |
HU: Hounsfield unit, SUVmax: Maximum standardized uptake value
| Imaging characteristics | Cut off value | Sensitivity | Specificity | AUC |
|---|---|---|---|---|
| SUVmax pleural fluid | ≥1.37 | 66.7 | 63.2 | 0.745 |
| HU pleural; fluid | ≥16.15 | 50 | 65.8 | 0.587 |
| SUVmax pleura | ≥3.05 | 66.7 | 73.7 | 0.746 |
| Pleural thickness | ≥5.5 mm | 66.7 | 71.1 | 0.706 |
AUC: Area under the curve, HU: Hounsfield unit, SUVmax: Maximum standardized uptake value
Onco 48: Evaluation of the effect of uricosuric agent (probenecid) on the pharmacokinetics of 68Ga-peptide based radiopharmaceuticals
Vikash Kumar Sahu, Ashok Chandak, Vikash Sahu, Sutapa Rakshit, Yogita Shete, M. K. Ray, Sandip Basu
Radiation Medicine Centre, BARC, TMC, Mumbai, Maharashtra, India
Introduction: Probenecid is a uricosuric drug that promotes the excretion of uric acid and clinically used in the treatment of gout. It is sulfamoylbenzoic acid derivative and acts on proximal tubules through the organic anion transporter. Most of the peptide-based molecules are excreted through kidney such as DOTA-TATE and PSMA-11. The effect of specific drug intervention using probenecid in order to improve the excretion and reducing the incidence of untoward advrse effects of the radiopharmaceuticals was studied in this work. Aims and Objectives: The present study was aimed to evaluate the effect of probenecid on the renal excretion of 68Ga-DOTATATE and 68Ga-PSMA11 in Wistar rats. Materials and Methods: The radiopharmaceuticals, 68Ga-DOTATATE and 68Ga-PSMA11 were prepared as per the standard protocols using E-Z automated module and examined in this experiment after QC. The premise was that if the probenecid (BENCID tablet) leads to excretion of radiopharmaceutical rapidly then the dose to the kidney will be reduced. The tablets were crushed and dispersed in WFI and were administered orally 0.2 mL (30 mg/kg) in healthy Wistar rats (225-250 gm) 30 mins. prior to injection of the radiopharmaceuticals. The radiopharmaceuticals (3-5 MBq) were injected (control and experimental) through tail vein of the animals. The imaging of the animals were done using Philips Gemini TOF-16 slice PET-CT scanner at 1 hr post-injection of radiopharmaceuticals (single time point). The ROI were drawn over each kidney and total counts were noted and subtracted from the background counts. Results: Percentage uptake was found 48 % and 52 % in right and left kidney respectively in experimental group which was 49 % and 51 % in control group at 1 hr PET imaging. There was no significant change in the images of the animal injected with 68Ga-DOTATATE and 68Ga-PSMA11 with and without probenecid. The preliminary results indicates that there is no significant change in the kidney excretion pattern in control and experimental groups. In this experiment we have used single point imaging due to short half-life of the radiopharmaceuticals. There is need to use long lived radiopharmaceuticals to find out the changes in the PK due to coadministration of probenecid with multiple time point imaging. Conclusion: The present study findings showed that the short-lived radiopharmaceuticals are not suitable to evaluate the change in PK effect using probenecid. Further studies will be carried out using 99mTc-HYNIC-TOC or 177Lu-DOTATATE with dedicated micro-SPECT imaging modality to evaluate the PK interactions.
Onco 49: Utility of PRIMARY score compared to SUV based assessment at initial evaluation of carcinoma prostate
Suraj Kumar, Y. Mathur, R. Kumar, H. Singh, B. Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: Multiparametric MRI is currently recommended by EAU-ASTRO guidelines prior to biopsy in case of carcinoma prostate. It is shown to have a high NPV by various trials, but is seen to have a low specificity leading to unnecessary biopsies. PSMA PET/CT in the PRIMARY trial which relied on a SUV based parameter also demonstrated low specificity. However, the PRIMARY score analyzed in the same cohort of patients, showed an improvement in specificity. The current study aims to compare the diagnostic performance of PRIMARY score, mpMRI and SUV based cut off in the detection of carcinoma prostate. Materials and Methods: Patients referred to the Department of Nuclear Medicine, PGIMER, Chandigarh with clinical suspicion of carcinoma prostate (with or without undergoing prior biopsy) between Jan 2021 to Dec 2022 were retrospectively reviewed. The lesion SUV max and PRIMARY score in these patients were analyzed and mpMRI results whenever available was collected. These patients were followed for at least 6 months for confirmation of diagnosis (Malignant vs Benign) based on TRUS/PET guided biopsy findings and/or follow-up serum PSA levels. Sensitivity and specificity were calculated and the AUCs were compared for the diagnostic accuracies of the modalities. Results: Of the 479 men, with mean age of 67.1 (±8.5) evaluated in the study, 70.5% (338/479) patients had carcinoma prostate. PRIMARY score-1 was seen in 16.2% (78), score-2 in 12.5% (60), score-3 in 3.5% (17), score-4 in 15% (72) and score-5 in 52.6% (252). The proportion of patients with ca prostate among PRIMARY score 1 to 5 was 15.3% (12/78), 16.6% (10/60), 64.7% (11/17), 83.3% (60/72) and 97.6% (245/151) respectively. SUV max values respectively among the PRIMARY score 1-5 were 5.0, 6.5, 7.4, 8.6, 27.6. Sensitivity, specificity for PRIMARY score 1,2 (low-risk patterns) vs PRIMARY score 3-5 (high risk patterns) was 92.7 and 82.6% SUV cut off ³4 showed a sensitivity and specificity of 98.5 and 15.9%. A lesion SUV max cut off of 9.2 was determined based on ROC analysis and showed a sensitivity and specificity of 81.3 and 88.8%. Sensitivity and specificity of PIRADS calculated in 223 patients was 80.6 and 71.6%. AUC for PRIMARY score, SUV> 9.2 and PIRADS was 0.92, 0.91 and 0.81 respectively with a significant difference in AUC of 0.11 (p < 0.05) and 0.10 on comparison of PRIMARY score and SUV> 9.2 with PIRADS respectively. The difference between PRIMARY score and SUV cut off was 0.01 (p = 0.2). Conclusion: PRIMARY Score was able to accurately identify patients who were seen to have ca prostate and showed a higher specificity compared to MpMR and SUV cut off ³4. PRIMARY score can be used as an effective tool in initial assessment of patients suspected to have prostate cancer prior to biopsy.
Onco 50: [18F] AlF-NOTA-NAC -Indirect radiofluorination using metal-based radiochemistry for development of L-type/ASC targeting system for glioma imaging
Kirti Dhingra, Sukhvir Singh, Nitin Kumar, Baljinder Singh, Anil K. Mishra, Puja P. Hazari
Advanced Radioisotope Production Center, Institute of Nuclear Medicine and Allied Sciences, Delhi, India
Introduction: Positron Emission Tomography (PET) using radiolabeled amino acids holds great promise in the detection and differentiation of glioma recurrence, residual disease and radiation necrosis. Due to the overexpression of amino acid transporters (LAT and ASC type) in the oncogenic proliferating cells (in Glioma) as carriers for the transport of amino acids, many AAs and their derivatives are labeled with radioisotopes as tumor imaging radioactive probes for PET/SPECT imaging. N-acetyl cysteine (NAC) can potentially serve as an amino acid PET tracer for tumor imaging. The aim of this study was to assess the feasibility of the Indirect radio fluorination using metal-based radiochemistry. We have synthesized NOTA-conjugated amino acid derivative NAC complexed with cold 19F, to check the stability of the compound, so that we can further subjected it to radiolabeling with 18F as a promising PET imaging agent [18[F]AlF-NOTA-NAC using the aluminium-[18F]fluoride ([18F]AlF) indirect radio-fluorination method with the convenience of metal-based radiochemistry, toward L-type and ASC amino acid transporter systems in the Brain oncogenic cells. Materials and Methods: Synthetic strategy utilized S-alkylation of N-acetyl Cysteine (NAC) with a chloroacetylated derivative of NOTA macrocycle to form NOTA-NAC complex. The [19F]AlF was formed by reacting 1 ml AlCl3 solution (0.02M) with 1ml KF (0.1M) in an NaOAc Buffer (pH 4-5), which firmly bound to Al3+ forming [19F]AlF, which can form complexes with different chelates. The stable [19F]AlF-based conjugate was formed with an N3O2 donor of NOTA bound to NAC, by heating at high temperature (100–120 °C) for 30 minutes in the reactor vial. Solution was filtered and evaporated under reduced pressure and then characterization of the product was done by Mass Spectroscopy and NMR and then HPLC was also performed. Results: NAC (biomolecule) was conjugated to hexadentate NOTA ligand via S-alkylation from the thiol side. Conjugation of the bio-vector was confirmed by the characterization technique using 1H-NMR spectra and Mass Spectroscopy. 19F cold labeling of chelating agent-biomolecule conjugates using the [19F]Al-F metal complexation based radiochemistry approach, formed a thermodynamically stable bond and kinetically inert, which further will be radiolabeled with [18F]AlF as a PET Brain targeting probe. In [19F]AlF-chelator complex, [19F]AlF2+ formed pentadentate ligands as one coordination site was occupied by [19F]fluoride. Conclusion: The aluminium-[18F]fluoride ([18F]AlF) indirect radiolabeling method combines the favorable decay and radiochemical characteristics of fluorine-18 with the convenience of metal based radiochemistry. Thus, the successful and stable cold 19F labelling of chelating agent-biomolecule conjugate would increase the possibility of 18F radiolabeling of the conjugate in the automated synthesizer module. So, [18F]AlF- biomolecule conjugates will be developed further for future discovery and development of radiotracers for diagnosis of disease target.
Onco 51: 68Ga-PSMA-PET/CT in patients with biochemical prostate recurrence after radical prostatectomy
Rajbir Mehra, Vijay Singh, U. P. Singh, Sanjoy Surekha, A. H. Naazar, Manish Ora, Sanjay Gambhir
Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: Prostate cancer remains one of the prevalent malignancies affecting men worldwide. Its occurrence is predominantly observed in older, underscoring the importance of early detection and management. Treatment modalities are available based on the patient's age, risk factors, and stage. It includesorchidectomy, radical prostatectomy, androgen deprivation therapy, radiotherapy, brachytherapy, chemotherapeutic agents, radionuclide therapies, and targeted immunotherapy. Radical prostatectomy represents a curative approach in localized cases. Post-surgery continuous follow-up with serum PSA is required to detect early recurrence. Biochemical recurrence is elevated PSA levels above 0.2 ng/mL after radical prostatectomy. Accurate and timely identification of biochemical recurrence is vital for management. 68Ga PSMA PET/CT is a novel imaging modality that has shown promising results in detecting and staging prostate cancer, especially in patients with biochemical recurrence after radical prostatectomy. However, the diagnostic performance of 68Ga PSMA PET/CT in this setting is still under investigation. It may vary depending on the PSA level, the Gleason score, the time interval since surgery, and anti-androgen therapy. In our study, we assessed the diagnostic efficacy of 68Ga PSMA PET/CT in detecting pathological lesions subsequent to biochemical recurrence. Materials and Methods: We did a retrospective study of 66 patients who had undergone radical prostatectomy and are having a biochemical recurrence. We obtained their data from the hospital registry and analyzed their demographic details, serum PSA levels, and 68Ga PET/CT findings. We divided the study population into groups based on rising serum PSA levels and the recurrent lesionlocation. Chi-square tests and other statistical analyses were performed to examine the association between serum PSA levels and lesion detection rates. Results: The patients had a mean age of 68.3 years (range: 51-83) and a mean PSA level of 20.35 ng/mL (median: 1.54 ng/mL, IQR: 0.61 – 4.16, SD: 114.6) at the time of recurrence. The overall detection rate was 63.6% (n = 42). The commonest recurrence site was the operative bed (39.4%), followed by regional nodes (36.4%) and distant lymph nodes (13.6%). Skeletal (24.2%) and other distant metastases (4.5%) were also noted. Serum PSA levels were <1.0 ng/mL (n = 28, 42.4%), ≥1.0 to 4.0 ng/mL (n = 21, 31.8%), and >4.0 ng/mL (n = 17, 25.7%), respectively. The detection rate increased with higher PSA levels, i.e., 25% for PSA <1.0 ng/mL, 85.71% for PSA ≥1.0 to 4.0 ng/mL, and 100% for PSA >4.0 ng/mL. The recurrence sites also differed among PSA groups. In patients presenting with PSA <1.0 ng/mL, the most typical common recurrence site was the operative bed (14.28%), followed by regional lymph nodes (10.7%), distant lymph nodes (3.57%), skeletal system (3.57%), and other distant metastases (3.57%) respectively. In the ≥1.0 to 4 ng/mL group, recurrence was observed in the operative bed (52.38%), regional nodes (42.85%), distant nodes (19.04%), skeletal system (23.8%), and other distant metastases (4.76%). In the >4.0 ng/mL group, recurrence was noted in the operative bed (64.7%), regional nodes (70.58%), distant nodes (23.52%), skeletal system (58.82%), and other distant metastases (5.88%). Pearson chi-square and point biserial correlation analyses revealed that PSA values were not significantly associated with distant nodal or other distant metastasis recurrence (p-value = 0.114 and 0.935, respectively). However, PSA values had a good positive correlation with recurrence in the operative bed, overall recurrence, recurrence in regional nodes, and skeletal metastases recurrence (p-value <0.05). Conclusion: Our study demonstrated that 68Ga PSMA PET/CT is a sensitive and specific modality for detecting biochemical recurrence of prostate cancer after radical prostatectomy. The recurrence site is detected in one-fourth of the patients with los S PSA(<1 ng/ml). The detection rates increase significantly once the S PSA > 1 ng/mL. PSA levels did not predict distant nodal (more than 50% of patients) or other distant metastasis recurrence. These findings highlight the importance of whole-body functional imaging to rule out recurrence at distant sites, which precludes the local radical treatment after biochemical recurrence in prostate cancer.
Category: Others
Other 1: Preparation and preclinical evaluation of 99mTc-glibenclamide formulation for detection of pancreatic problems
M. K. Ray, Ashok Chandak1,2, Sajid Husain1, Sutapa Rakshit1, Yogita Shete1, M. K. Ray1, Sandip Basu1
1Radiation Medicine Centre, BARC, Mumbai, Maharashtra, 2Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, Haryana, India,
Introduction: Diabetes mellitus is result of an absolute or relative reduction in pancreatic beta cell mass leading to insufficient secretion and hypoglycemia. Treatments for diabetes mellitus range from drugs that increase insulin secretion and sensitivity, to insulin administration, to pancreatic islet cell transplantation. Glibenclamide (GBD) is one of the most potent sulfonylurea derivatives used in the treatment of maturity-onset diabetes by inducing insulin secretion in pancreatic β cells. Pancreatic islet cell mass (PICM) is a major element of the insulin secretory capacity in humans which is examined by invasive study. The pancreas is deep in the middle of the body so it is difficult to image with CT and also critical for biopsy. Noninvasive procedures are needed to quantify beta cell mass for monitoring the onset, progression and responses to therapy and to detect rejection in transplant patients. The present work was aimed to assess the pancreatic beta cell in normal healthy rat (animal) using SPECT-CT imaging. Objective: The aim of the present study was to use inhouse optimized stable 99mTc-GBD preparation for imaging of pancreatic glands noninvasively specially the islet cell mass. Materials and Methods: The optimization of the formulation was carried out using different ratio/concentration of the solvents such as PEG 400, ethanol and DMSO and reducing agent SnCl2 .2H2O in the preparation. 10 mCi (± 1.0) 99mTc were added to the drug solution and heat the vial in boiling water bath. Carried out the physicochemical and biological quality control test of the labeled product. Biodistribution studies were carried out of optimized product injected (5 MBq) into the teil vein of the healthy normal Wistar rat and SPECT-CT imaging was done at 45 min 6 hr and 18 hr post injection. Results and Discussion: The product was found clear with pH 5.0 (± 0.2) and obtained reliable overall radiochemical yields and RCP without any chelating agent coupling with GBD. The in-vivo study of normal animal confirms the stability and shows that the drug is deposited very specifically at the pancreas. Conclusion: The 99mTc-GBD is promising RP for imaging the pancreatic islet cell mass and to detect the problems in the initial stage of the disease noninvasively. for imaging of the pancreas is under progress. Standardization of dose in pancreatic tumor animal model evaluation will confirm the utility of the labeled product.
Other 2: Indigenous sourcing of [177Lu]LuCl3radiopharmaceutical ingredient for use in targeted radionuclide therapy – A major step towards self-reliance
K. V. Vimalnath, Sharad P. Lohar, Priyalata Shetty, Sourav Patra, Sudipta Chakraborty
Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
Introduction: In recent times, with significant increase in the number of 177Lu-DOTATATE and 177Lu-PSMA therapies in India, the requirement of [177Lu]LuCl3 radiopharmaceutical precursor with adequate specific activity and purity has increased to a great extent. To ensure uninterrupted supply of [177Lu]LuCl3 to cater this enhanced requirement, availability of Lu target with isotopic enrichment of 176Lu at 75%or higher in adequate quantity is absolutely essential. So far, the target material is being imported at a very high cost and also imports are inconsistent. It is therefore felt necessary to develop in-house technology to produce isotopically enriched target of 176Lu to achieve self-reliance in sourcing of [177Lu]LuCl3 in India. The present abstract describes the clinical translation of [177Lu]LuCl3 radiopharmaceutical precursor produced using target material produced in-house. Materials and Methods: Laser based isotope selective excitation followed by ionization and collection using electromagnetic fields (ATLA facility, BARC) have been used to enrich natural Lu (2.6 atom% 176Lu) to the extent of 80-90 atom% of 176Lu. Aliquots of isotopically enriched (more than 80% in 176Lu) Lu(NO3)3 were deposited over quartz boat (typically 1.0-1.5 mg Lu), dried, sealed in standard 1s Al can and irradiated at ~1.4×1014 n/cm2/s thermal neutron flux in Dhruva research reactor for 14 d. Irradiated targets were radiochemically converted to [177Lu]LuCl3 solution. Quality parameters such as radionuclidic purity, radiochemical purity and chemical purity of the [177Lu]LuCl3 formulation were checked to ascertain its suitability for clinical use in accordance with quality control monogram approved by DAE-RPC. Ready-to-use therapeutic doses DAE-RPC approved radiopharmaceuticals such as, [177Lu]Lu-DOTATATE and [177Lu]Lu-PSMA were prepared and evaluated for their suitability for human clinical use. Results: Radiopharmaceutical precursor [177Lu]LuCl3 was produced by direct activation route with 21.6 ± 1.8 Ci /mg specific activity by 14 d irradiation protocol at highest available thermal neutron flux of Dhruva research reactor. Results of quality control tests showed that the formulation is suitable for preparation of radiopharmaceuticals for clinical use. Ready to use therapeutic doses of [177Lu]Lu-DOTATATE and [177Lu]Lu-PSMA prepared using [177Lu]LuCl3 qualified for use in patients conforming to the RPC requirements of radiochemical purity >97% and radionuclide purity of >99.9% at the time of administration. Based on these studies, total around 50 Ci [177Lu]LuCl3 formulation were subsequently produced in 11 batches using indigenously prepared enriched Lu target and deployed for treatment of patients in major nuclear medicine centers all over India namely, RMC, Mumbai, TMH, Mumbai, AIIMS, New Delhi, PGIMER, Chandigarh, Jaslok Hospital Mumbai and JIPMER Puducherry. Conclusion: In-house production of isotopically enriched 176Lu target (80-90 atom%) is a major achievement towards realising self-reliance in indigenous sourcing of [177Lu]LuCl3 radiopharmaceutical precursor for targeted radionuclide therapy in India. Radiopharmaceutical grade [177Lu]LuCl3 formulation produced from indigenous target has been successfully utilized in treatment cancer patients in major nuclear medicine centers across India by formulation of therapeutic radiopharmaceuticals namely, [177Lu]Lu-DOTATATE and [177Lu]Lu-PSMA.
Other 3: Exploring the possible correlation between TC-99m thyroid uptake and 24 Hr. I-131 uptake
Manisha Pradhan, Satyawati Dewal, A. K. Shukla
Department of Nuclear Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: The alteration in thyroid hormonal profile results into host of disorders including Graves’ disease which is an autoimmune disorder caused by excess production of thyroid hormones and accounts for about (50-80) % of all cases of thyrotoxicosis. The present study was conducted to ascertain a correlation between thyroid uptake of Tc-99m and I-131 in 20 cases of Graves’ disease. Materials and Methods: Retrospectively performed thyroid scan by using 99mTc (3-5) mCi under DISCOVERY NM/CT 670SERIES SPECT/CT and thyroid uptake study using I-131 50uCi capsule by CAPINTEC 4000e thyroid probe and a leucite neck phantom in 20 patients of Graves’ disease reporting to the department of Nuclear Medicine, DR RMLIMS, Lucknow. Studies were performed 20 minutes after intravenous injection of 99mTc-pertechnetate and images were obtained on dual head SPECT gamma camera. The ROI were drawn on thyroid gland and background to compute the no. of counts. After applying decay correction, the % uptake was calculated by:
% uptake = [(thyroid count - background count)/ (pre-injection syringe count-post injection syringe count)] × 100%
For thyroid uptake using I-131, the dose was administered orally and scintillation probe was used for thyroid uptake measurements at 25 cm at 0 hour, 4 hrs., and 24 hrs. respectively.
The I-131 Uptake % = (Neck count – thigh counts)/ (standard counts background) *100.
Results: The Tc-99m uptake was observed to be ranging from 2.10% to 43% whereas I-131 uptake ranges from 11.8% to 107.70%. The coefficient of correlation, r indicated no correlation between the two studies suggesting there is no linear correlation or link between the variables. Conclusion: The study shows negative correlation between Tc99m scan and 24 hr. I-131 uptake values. However, it would be appropriate to undertake such a study with larger no. of cases to predict whether any of these two can be used in an alternative manner as a method for deciding therapeutic doses in cases of Graves’ disease.
Other 4: Clinical evaluation and quantification of gastroesophageal reflux by non-invasive scintigraphy technique in patients using liquid as well as capsule methods
Amandeep Kaur, Dr. Pritam Singh Soni, Dr. Gurmeet Kaur, Dr. Divya Soin
Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India
Introduction: The Gastroesophageal Reflux Scintigraphy (GERS) approach has the potential to be more efficient, non-invasive, and convenient than existing imaging techniques. The sole disadvantage of the GERS technique is that its liquid nature causes contamination of the whole esophageal lining, making it difficult to interpret low-volume reflux appropriately. On the other hand, the use of gelatine capsules to encapsulate radioactivity reduces the risk of esophageal lining contamination. Taking into account the aforementioned considerations, a prospective study was carried out on the clinical evaluation and quantification of gastroesophageal reflux (GER) using a non-invasive syntigraphic technique. Furthermore, we assess the efficacy of the radioactive liquid method and the radioactive capsule method in terms of providing better and more accurate scans. Materials and Methods: The present study included all symptomatic patients who were sent to the Department of Nuclear Medicine for Gastroesophageal Reflux Scintigraphy (GERS) imaging. Patients underwent the GERS technique in three different ways, taking into consideration their age, medical history, and physical condition. These approaches included ingesting the liquid via a nasogastric (NG) tube, drinking the radioactive liquid directly, or taking radioactivity in a gelatin capsule with a small quantity of water. Following the GERS, each imaging image was thoroughly analysed, including both qualitative and quantitative interpretations. This evaluation was carried out using a standardised scoring system specifically designed for scintigraphy assessments. Results: The study included 95 people with an age range of 2.5 months to 71 years: 54 men (5 months to 70 years) and 41 women (5 months to 71 years). According to static image processing and viewing in cine mode, 73/95 patients (43/54 men and 30/41 females) had a spike in esophageal activity or were GER-positive. Moreover, GERD is more prevalent in men while they are young but becomes more common in women after the age of 40. A significant percentage of individuals (42.0%) had a low body weight; 93.75% of these people had GER, while 86.66% had grade III reflux. In addition, 26.31% were obese, 65.38% had GER, and 64.7% had Grade III reflux. According to the present study's results, a significant majority of participants, 84.9%, who were diagnosed with GERD, had reflux episodes within 15 minutes or before stomach emptying (GE t1/2). The average time for capsule breakage to occur was 3.63 minutes, with a range of 2 to 6 minutes. The entire capsule breaking time was 5.0 minutes on average, with a range of 4 to 7 minutes. Conclusion: The prevalence of GERD varies across genders and age groups. Weight gain and GERD were shown to have a statistically significant positive association in the study. Furthermore, a link was found between GERD after gastric emptying (GE t1/2) and a drop in body weight percentile at this time. Furthermore, the capsule method improves the efficiency of the scintigraphy technique by reducing esophageal contamination, enhancing scan quality, and allowing for the examination of low-grade reflux. A lung imaging study also revealed the presence of a radiotracer in three infants and one adult, indicating aspiration pneumonia.
Other 5: Radiation safety challenges in security screening: For distinguishing active patient traveler from illicit transport of radioactive materials
S Pathak, B. Shimja, P. Tandon, P. K. Dash Sharma
Atomic Energy Regulatory Board, Mumbai, Maharashtra, India
Introduction: In Nuclear Medicine (NM), unsealed radionuclides are administered to patients for imaging as well as therapy. Despite low activity used for NM-Imaging, patients may emit detectable radiation as they return home post-procedure. Activity administered for NM therapy is few order higher as compared to diagnostic procedures. Whereas, in brachytherapy (a form of Radiotherapy), sealed source are implanted to treat cancers. Sensitive radiation detectors are installed at major sea-ports, airports and land boarders in India. Subsequent to NM procedures, residual radioactivity in patient might trigger these detectors. Further, there is likelihood of contamination of belongings of the patient, even though radiation levels are very low. NM patients being held at Indian airports have been reported in recent time. Security official engaged in screening must distinguish medical use from illicit transport of radioactive materials. This necessitates a study to address this concern by bringing a comprehensive procedure for the same. Materials and Methods: We conducted a holistic review of current regulations for discharging patients following radionuclide procedures. A survey was conducted with 10 hospitals nationwide that perform such procedures. Further, an in-depth literature review was conducted to gather insights from international best practices. Using these as input, a procedure is developed for security officials. Results: Procedure to be followed by Security officials:
Once the radiation detector gives an alarm/ indication, radiation level at 1m from the individual should be checked
If the radiation level at 1m is below 50 µSv/h (i.e 5mR/h) from an individual or his belongings, there is a likely hood that the radiation is due to some medical procedures with radionuclides
In case of radiation levels more than 50 µSv/h, DAE-ECR may be consulted for further action
If the radiation is not from the individual it might be from his/her belonging. Check the belonging for plausible contamination and segregate the contaminated materials. If no contamination found, the case need to be investigated in detail
If, the individual informs that the radiation is from medical procedure, ask for the travel card issued by the hospital at the time of discharge
If required, the contacts mentioned on the card may be contacted for further clarification w.r.t. to the medical procedure undergone by the individual.
Further a clear delineation of the roles and responsibilities NM Physicians/RSOs, and patients is essential for effectively deal with such incidences.
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Role of the NM Physician/ RSO:
Prior to administering the activity, counsel the patient about the possible issues that may come across during their travel after the therapy
Provide the patient with travel card that have the information such as patient name, date of treatment and discharge, radiation level @ 1m from the patient at the time of discharge, contact number of concerned Physician/RSO etc
At the time of discharge, the RSO should ensure that belongings of the patient are free from radioactive contamination
Provide inputs to the security official w.r.t. the radionuclide procedure as and when needed
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Role of the patient:
1.. Carry the travel card during traveling subsequent to radionuclide procedures
2.. If required, explain the airport officials about the treatment received and support them by producing the travel card
3.. Arrange to get all the personal belongings used during the treatment checked for contamination before leaving the hospital.
Conclusion: It is imperative, that security officials must distinguish medical use from illicit transport of radioactive materials. The developed procedure will be helpful for security officials for the same. It also brings out the cooperation needed from NM professionals for minimizing the hustle at security checkposts at sensitive areas like airports, ensuring a smoother and more efficient screening process for travelers and enhancing overall security measures.
Other 6: 99m Tc- DTPA- Glomerular Filtration Rate estimation in south Indian population
S. Sabari Nathan, Dr. K.K. Kamaleshwaran, Dr. E. Ramkumar, Radhakrishnan, Dr. Arun pandian, F R Kingsley, Sowmya, Ruth R, Suvalakshmi, Rithika
The TamilNadu Dr. MGR Medical University
Introduction: The normal range is 80-120 ml/min. Various available methods are serum creatinine tests, inulin clearance test, using Cr51-EDTA and plasma sample method. Though inulin clearance is considered as a gold standard for GFR estimation, it is complex to perform and it is expensive and time consuming and requires a steady state plasma concentration. The other methods are non-accurate, less availability and increase in radiation exposure and time consuming while an alternative equivalent method which is technetium labeled with DTPA estimates GFR in a minimal time and has less radiation exposure and it does not alter the renal function and it is non- toxic.
Materials and methods:
Equipment: Symbia T-True point SPECT CT equipped with SYNGOP workstation
Methodology: 99m Tc –DTPA was prepared as per the BRIT protocols. Pre syringe counts are taken and a dose of 3-5 mCi is administered to the patients and followed by dynamic acquisition for 6 minutes of distribution and clearance of radiotracer using a dual head gamma camera equipped with low energy high resolution collimator. Post syringe counts are taken and Time Activity Curves are obtained. Images are acquired and ROI was drawn and GFR was estimated for different age groups (20-60) using gates formula.
Results: Estimated average GFR for different age groups -The average GFR for patients of age group (20-60) in south India is 93.5ml/min.
Conclusion: This study provides reliable GFR value for patients of various age groups ranging from 20-60 in south India by using 99mTc-DTPA and gates method in a minimal time.
| Age | Total patients | Average GFR |
|---|---|---|
| 20-30 | 20 patients | 93.2 ml/min |
| 31-40 | 40 patients | 93.4 ml/min |
| 41-50 | 57 patients | 90.9 ml/min |
| 51-60 | 75 patients | 96.8 ml/min |
Other 7: BERT-T-stage lung carcinoma classifier: A preliminary study
Sneha Mithun, S. Mithun, A. K. Jha, U. B. Sherkhane, V. Jaiswar, B. Nath, A. Tripathi, G. M. Mehta, S. Panchal, V. M. Noronha, K. Prabhash, N. C. Purandare, V. Rangarajan, S. Puts, A. Dekker, L. Wee
Department of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands
Introduction: Imaging reports are used for clinical staging of cancer. Clinical stage at the time of diagnosis plays an important role in disease prognostication and treatment planning. It also helps with objective assessment of disease progression during interim assessment or follow-up. AJCC (American Joint Committee on Cancer) TNM staging is widely used for lung carcinoma clinical staging, where T represents the size and extent of primary tumor, N represents the lymphatic spread of cancer and M represents the metastatic spread of cancer. In this study we have used pre-trained BERT model for assigning T-stage (T1, T2, T3 and T4) from lung carcinoma radiology reports. Materials and Methods: Study was approved by the institutional ethics committee as retrospective study with waiver of consent. 221 lung carcinoma imaging reports (PET/CT & CT) with initial diagnosis were used. This data was divided into 4 classes, namely, T1 (9.69%), T2 (38.77%), T3 (23.35%), T4 (28.19%) and no reports with T0. The T stages were assigned to the reports by experienced clinicians as per AJCC TNM 7th edition and extracted from the hospital information system. We performed a random stratified train–test split (70:30) of the corpus. Training set was used to fine-tune the BERT model which was then assessed using the test set. Macro-average area under receiver operating curve (AUROC) as well as AUROC for individual class was determined. Results: BERT-T-stage lung carcinoma classifier AUC of the macro-average ROC on test was 0.64, and for individual classes were 0.60, 0.62, 0.51, and 0.78 for T1, T2, T3 and T4 respectively.

Conclusion: This preliminary study shows that pre-trained BERT models have potential to be used for deriving some tumor stage information from radiology reports; however future work needs to focus on improving the data preparation steps and significantly increasing the sample size for training.
Other 8: Assessment of correlation between renal cortical thickness and estimated differential renal function in paediatric patients
Naincy Golus, Satyawati Deswal, Shashwat Verma, Ajai Kumar Shukla
Department of Nuclear Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: The prevalence of renal impairment has been found to be increased worldwide in paediatric patients. In order to have first-line evaluation of patients, S. creatinine test is usually performed. On the other hand, USG of patients is done to morphologically assess renal cortical thickness which can also work as a prognostic factor. A recent study suggests that progressive decrease in cortical thickness might be an early sign of renal dysfunction. The present study was undertaken to evaluate the relationship between renal cortical thickness measurements obtained in real time by USG and differential renal function obtained from Tc-99m labelled EC Scan. Materials and Methods: In this retrospective study, 26 paediatric patients reporting to department of nuclear medicine at this institute who were referred for renal function EC Scan were included. EC Renal scan was performed on discovery NM/CT 67 dual headed gamma camera after administering 74-148 MBq of Tc-99m labelled EC radiopharmaceutical and their differential renal function was estimated using standard imaging and processing protocol and their recent s. creatinine reports were also taken into consideration. Inclusion criteria for patients included patients aged less than 12 yrs of age and of either sex with established clinical diagnosis of hydronephrosis. USG Scans were performed by Radiologist and renal cortical thickness were measured in the sagittal plane above the medullary pyramid perpendicular to the capsule in upper, mid and lower third of kidney. Patient scans were categorized into five groups based on their differential function status- A-Normal having 7 patients B- Mild having 6 patients C- Moderate having 6 patients D- Severe having 3 patients E- Poor having 4 patients and correlated with their cortical thickness. Results: This sample of study includes 26 patients. The mean age was 3.84 years (range – 0.15-11 years: SD = 3.27 years). The average level of S. creatinine was 0.79 mg/dL (range = 0.35-2.02 mg/dL, SD = 0.49 mg/dL). Pearsons linear correlation coefficient (r) showed very good correlation for normal group between measurements of cortical thickness and differential renal function in right (r = 0.73) and left kidney (r = 0.86), for mild group- right(r = 0.35) and left (r = 0.68),for severe group- right (r = 1) and left kidney (r = 0.76), for poor group- right (r = 1) and left kidney(r = 0.98) but shows no correlation in moderate group for right (r = -0.13) and left kidney (r = -0.37). Conclusion: The results of this study demonstrate that the renal function was well correlated with renal cortical thickness obtained through USG scan However USG measurements are operator dependent and cannot be independently used as predictor for renal function as seen in a subgroup of patient.
Other 9: Correlation of gated SPECT-CT myocardial perfusion imaging with echocardiography for the measurement of left ventricular ejection fraction in patients with chronic kidney disease
S. Enusiya, K. K. Kamaleshwaran, E. Ramkumar, E. R. Radhakrishnan, F. R. Kingsley, Arun Pandiyan, M. Swomya, R. Ruth, R. V. Suvalakshmi, Rithika
Department of Nuclear Medicine, The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India
Introduction: MPI SPECT-CT is used to evaluate myocardial perfusion. Almost all the patients who undergo MPI SPECT-CT have previously done echo. The aim of this study is to correlate the LVEF values between MPI SPECT-CT and echo. Materials and Methods: Reports of 60 patients with CKD who were referred for gated SPECT –CT MPI was analysed. Similarly the echocardiograghy reports of following patients were interpreted. Quantification of EF was performed by using quantitative gated SPECT (QGS) (QGS – version 2010) on symbia -T-true point SPECT-CT equipped with SYNGOP workstation. Results: On finding average mean of LVEF for 60 patients in myocardial SPECT-CT and echocardiography, it is found that on an average results in echocardiography were 54% and myocardial SPECT were 52%. By finding the difference in two studies by averaging it is found that LVEF deviates by 2% between echo and gated SPECT -CT MPI. Conclusion: A good correlation was found between echocardiology derived LVEF and the values derived using gated SPECT-CT MPI (QGS). Thus it can be concluded that SPECT -CT MPI can be effectively used to assess LVEF compared with echocardiography.
Other 10: A retrospective analysis to differentiate between septic and aseptic loosening in three phase-bone scan
G. Kiran, K. K. Kamaleshwaran, E. Ram Kumar, E. R. Radhakrishnan, F. R. Kingsley, Arun Pandian, Suvalakshmi, R. Ruth, M. Sowmiya, R. V. Rithika
Department of Nuclear Medicine, The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India
Introduction: Three-phase bone scan is routinely employed to evaluate bone uptake and infection imaging in patients who had undergone prosthetic knee replacement. Symptoms of loosening are quite non-specific with persistent pain and reduced mobility at prosthetic site. When loosening is caused by infection it is called as septic loosening while loosening without infection can be classified as aseptic. Materials and Methods: EQUIPMENT: Symbia -T true point SPECT-CT equipped with Syngop workstation. Retrospective analysis of Three-phase bone scan image and reports of 27 patients who had undergone hip and knee replacement surgery was done to determine the status of prosthetic loosening. An increased uptake in blood flow, blood pool, and delayed phase is a characteristic of Septic loosening while a remarkably increased uptake in delayed phase is a characteristic of Aseptic loosening. Results: It can be interpreted from the results that bone scan is instrumental in distinguishing between
| Age | Region of prothesis | Number of patients | Prosthetic status (%) | Surgery and NM bone scan interval (mean) (years) |
|---|---|---|---|---|
| 50–60 | Hip and knee | 8 | Septic - 100 Aseptic - 0 |
3.2 |
| 60–70 | Hip and knee | 11 | Septic - 81.8 Aseptic - 18.1 |
2.3 |
| 70–80 | Hip and knee | 6 | Septic - 66.6 Aseptic - 33.3 |
2 |
| 80–90 | Hip and knee | 2 | Septic - 50 Aseptic - 50 |
1 |
NM: Nuclear medicine
Septic and Aseptic loosening. Conclusion: This study concludes that three phase bone scan is effective in evaluating Septic/Aseptic status of prosthetic loosening. Others scintigraphics like 99mTc-HMPAO labelled WBC'S and 18F-FDG PET can also be employed in infection imaging for more explicit results.
Other 11: A novel innovative technique which minimizes exposure to radiation professionals while dispensing 18F-FDG
V. S. Rupan Kumar, K. K. Kamaleshwaran, E. Ram Kumar, E. R. Radhakrishnan, F. R. Kingsley, Arun Pandiyan, M. Sowmya, R. Ruth, Suva Lakshmi, R. V. Rithika
Department of Nuclear Medicine, The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India
Introduction: Conventionally, 18F-FDG multi-dose vial is placed in the lead pot which reduces the exposure to the radiation professional and patient dose is dispensed from the vial via lumbar puncture needle. The aim of this study is to present a model which is significantly more efficient in minimizing exposure to radiation professionals while dose dispensation. Materials and Methods: A multidose vial was placed in the lead pot, lumbar puncture needle was inserted in the dose vial and a 3-way lock was attached to the hub of lumbar needle, followed by placing a lead enclosure on top the lead pot containing the activity vial. A dose of 4.4 mCi (162.8MBq) was withdrawn into a syringe and placed on top of 3-way lock. The exposure from the syringe is measured with and without the lead enclosure, around three points designated as A, B, and C in the L-bench. Results: Exposure was measured using survey meter in the L-bench,
| Points | With lead enclosure (µSv/h) | Without lead enclosure (µSv/h) |
|---|---|---|
| A | 0.70 | 1.30 |
| B | 0.30 | 1.10 |
| C | 0.90 | 2.60 |
Conclusion: The study concludes that addition of lead enclosure of thickness 30mm around the 3-way lock added to the withdrawal needle efficiently minimizes radiation exposure. Therefore, implementing this technique into practice effectively minimizes the absorbed dose to the radiation professionals.
Other 12: Stability analysis of lutetium-177 – Prostate-specific membrane antigen
Shalo Shaji, K. K. Kamaleshwaran, E. Ram Kumar, E. R. Radhakrishnan, F. R. Kingsley, Arun Pandian, Suvalakshmi, R. Ruth, M. Sowmiya, R. V. Rithika
Department of Nuclear Medicine, The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India
Introduction: Radiolabeled PSMA (prostate-specific membrane antigen) is a potential therapeutic target in the treatment of prostate cancer. 177Lutetium (177-Lu) is a beta-emitting radionuclide with a half-life of 6.65 days and beta energy (497kev, 384kev & 176kev) it is an excellent radionuclide for targeted radionuclide therapy. Oxidation state of this radionuclide (3+) necessitates the employment of multi-dentate chelators like DOTA to form a stable molecule. Materials and Methods: 200mCi of 177Lu PSMA was ordered from BRIT, Mumbai, for treatment of patients diagnosed with Prostate Cancer. Around 100 µL was pipetted to 10Eppendorf vials and each having 10µL. 5Eppendorf vials were stored in room temperature and rest in the refrigerator at 0ºC. RP was analyzed with freshly prepared solvent consisting of Acetonitrile and HPLC water in 1:1 ratio. The ITLC-SG paper was cut into 10×0.8 cm and marked 1cm away from both ends as the origin and solvent front. An aliquot of 177Lu PSMA sample was dropped at the origin. The chromatogram was developed. The strip was dried, cut into ‘point of spot’ & ‘solvent’ front, and counted. RP analysis was performed in 24 hour interval consecutively for five days. Results: The stability of 177Lu-PSMA was studied for 5 consecutive days from the date of receipt. 177Lu-PSMA was stable for 5 days and RP above 95% for both samples. Conclusion: The study concluded on the positive side emphasizing the stability of 177Lu-PSMA samples even after five days of receipt.
Other 13: A comparitive analysis of sentinel lymphnode scintigraphy in SPECT/CT and planar imaging in early breast carcinoma patients
B. Medhavardhini, K. K. Kamaleshwaran, E. Ramkumar, E. R. Radhakrishnan, F. R. Kingsley, M. Sowmiya, R. Ruth, R. V. Rithika, S. Arun Pandiyan, Suvalakshmi
Department of Nuclear Medicine, The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India
Introduction: Sentinel Lymph Node (SLN) scintigraphy is a routine technique in breast cancer management. This preoperative scintigraphy imaging plays crucial role in the process of SLN detection. The aim of this study is to verify whether routine performing of SPECT/CT in addition to planar imaging, increases the sensitivity of SLN detection in patient with early stage breast cancer. Materials and Methods: Equipment – Symbia Truepoint SPECT/CT equipped with Syngop workstation. A retrospective study of 68 early stage breast cancer patients of age group of (30yrs-85yrs) with (mean age -54) underwent lymph node scintigraphy from January – August 2023. 99mTc labeled Human Serum Albumin colloid in 3 alliquots with each (0.5mci) was injected intradermally in peri-areolar region before day or on the day of surgery. SPECT/CT and Planar imaging of the chest was done on day of surgery and identified number of nodes in three levels of axilla and informed to surgeon before surgery. Results: Among 68 patients, total 115 nodes are visualized in planar, but 160 nodes are visualized in SPECT/CT, among that 110 nodes were identified in level-I axilla, 42 nodes were identified in level-II axilla, 4 nodes were identified in level-III axilla, 3 nodes in intramammary, 1 in internal mammary region. SPECT/CT detects approximately 39% more nodes than planar imaging. In 13 patients no nodes were visualized in planar while in SPECT/CT showed SLN in all patients. In 4 patients, both planar and SPECT CT showed no nodes and methylene blue has identified nodes. Conclusion: The study concludes that SPECT/CT provides best anatomical details in delineating the level of nodes which assists the surgeons during surgery.
Other 14: Effect on intrinsic uniformity of gamma camera with varying in activity and volume
A. Dhanusha Sri, K. K. Kamaleshwaran, E. Ramkumar, E. R. Radhakrishnan, S. Dhayalan, F. R. Kingsley, M. Sowmiya, R. Ruth, R. V. Rithika, S. Arun Pandiyan, Suvalakshmi
Department of Nuclear Medicine, The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India
Introduction: Uniformity refers to uniform response of gamma camera throughout the field of view (FOV). Non-uniformity leads to artifacts in images. The study was performed to evaluate intrinsic flood uniformity response of gamma camera with increasing activity and volume of the point source. Materials and Methods: The collimator was removed from the camera and all possible sources from the room was removed and background radiation was checked. 99mTc point source was carefully placed in the source holder.
-
Constant activity & increase in volume:
Constant radioactive source of 35µCi is placed in the holder and the volume is increased by adding 0.9% sodium chloride (20 to 1000 µl at 20 µl intervals). Images were acquired for 10 million counts.
-
Increase in activity with constant volume :
The source activity is increased from10 to 500 µCi at 10 µCi intervals and image were acquired for 10 million counts.
Results: The acquired data was compared with the manufacturer's guidelines and it was observed that when source activity increased above 160 µCi showed significant variation on intrinsic uniformity. No variation was observed with increase in source volume on intrinsic uniformity. Conclusion: The study concludes that source activity of less than 160 µCi has no considerable effect on intrinsic uniformity. The source volume upto1000 µl has little or no impact on intrinsic uniformity.
Other 15: Synthesis and bio-evaluation of [177Lu]Lu-labeled Chlorambucil for targeted tumor-therapy
Naveen Kumar, Soumi Kolay, Mohini Guleria, Tapas Das
Department of Nuclear Medicine, Homi Bhabha National Institute, Mumbai, Maharashtra, India
Introduction: Chlorambucil, a well-known anticancer agent, finds regular use in the treatment of leukemia, lung, breast, and solid tumors. It exerts its chemotherapeutic effect through covalent bonding, culminating in the interlinking of nucleic acid chains or their attachment to proteins. Nevertheless, its restricted cellular permeability, non-specific targeting, and potential side effects have truncated its clinical utility. In nuclear medicine, the drugs or biomolecules are employed in the radiolabeled form in tracer amount wherein the drug acts as a targeting vector and facilitates the intracellular and/or nuclear penetration of the attached radionuclide for diagnostic or therapeutic application. This considerably reduces the drug dependent cytotoxic effects. In this line, attempts were made to explore the possibility of utilization of Chlorambucil as a radiotherapeutic agent for targeted therapy of solid tumors by designing and synthesizing a lutetium-177 complex of Chlorambucil. Materials and Methods: This work reports the synthesis, radiolabeling and preliminary biodistribution studies in tumor-bearing mice model for [177Lu]Lu-DOTA-Chlorambucil. DOTA-Chlorambucil derivative was successfully synthesized by conjugation of DOTA to Chlorambucil via N-Boc-ethylenediamine linker. All the intermediates and final products were purified and characterized by standard spectroscopic techniques viz. FT-IR, 1H/13C-NMR as well as by mass spectrometry. DOTA-Chlorambucil was radiolabeled with a therapeutic radionuclide viz. 177Lu [T1/2 = 6.73 d, Eβ(max) = 497 KeV, Eγ = 208 (11%), 113 (6.4%)] using optimized protocol (incubation for 45 min at 90°C in 0.2M NaOAc buffer at pH = 5.6). The percentage radiolabeling yield was determined using RP-HPLC. Partition coefficient (Log Po/w) was determined for the radiolabeled complex using octanol-water bi-phasic solvent system. Biological behavior of radiolabeled Chlorambucil derivative was investigated in fibrosarcoma bearing Swiss mice model wherein accumulation of radiolabeled agent in different organs including tumor was evaluated at two different post-administration time points viz. 2 and 24 h. Results: DOTA-Chlorambucil derivative was synthesized in near quantitative yield and structural modifications were confirmed via spectroscopic techniques. [177Lu]Lu-DOTA-Chlorambucil could be prepared with a radiochemical purity of > 90% under the optimized protocol. A partition coefficient of -2.30 was observed for [177Lu]Lu-DOTA-Chlorambucil. As per the results of bio-distribution studies, [177Lu]Lu-labeled-DOTA-Chlorambucil exhibited less uptake and rapid clearance from majority of the organs including tumor (1.01 ± 0.13 and 0.34 ± 0.03 % IA/g at 2 and 24 h post-injection). Conclusion: DOTA conjugation substantially heightened hydrophilicity (as indicated by LogPo/w value) of the [177Lu]Lu-DOTA-Chlorambucil complex, expediting drug elimination from the body and resulted in a relatively compromised tumor uptake.
Other 16: Evaluation of biodistribution and dosimetry of indigenously prepared 177Lu-DOTA-trastuzumab in HER-2 positive metastatic and locally advanced breast carcinoma
Yoga S. Narwadkar, Rahul Parghane, Sudeep Sahu, Sangita Lad, Kamaldeep, Sudhir Gupta, Tejal Suralkar, Sandip Basu
Radiation Medicine Centre, BARC, HBNI, Mumbai, Maharashtra, India
Introduction: Breast carcinoma is the most common malignancy among women globally, with an increasing incidence in India. About 25% of breast cancer is HER2-positive, which is an aggressive subtype. The management of HER2-positive breast cancer has improved with the introduction of targeted therapies like trastuzumab. Radioimmunotherapy, which uses radionuclides conjugated to tumor-directed monoclonal antibodies, is a promising approach to further improve treatment outcomes in breast cancer. Materials and Methods: The study prospectively evaluated HER-2 positive metastatic/locally advanced breast carcinoma patients who received dosimetric dose of 177Lu-DOTA-Trastuzumab. Patients first received Trastuzumab 25 mg/m2, followed by a diagnostic dose of 185-370 MBq of 177Lu-DOTA-Trastuzumab via intravenous infusion in 0.9% normal saline over 15-20 minutes. Serial whole body (WB) planar images were obtained on gamma camera soon after the infusion at multiple time points at pre-void and post-void post-infusion (P.I.); 24 h (P.I); 72/96h (P.I). WB and organs ROI (region of interest) were drawn and numbers of disintegrations were obtained. Mean absorbed dose for liver, spleen, kidneys, heart, red marrow, and tumor were obtained from OLINDA EXM v2.1.1 and ORIGIN software. Results: A total of 21 female patients were included and analyzed in this study. Biodistribution analysis showed tracer activity in the physiological organs (liver, spleen, kidneys, heart, and red marrow) and in tumor lesions. The maximum number of patients (n = 12) showed two components of clearance, namely fast and slow. Average effective half-life of all the patients (including single and two components of clearance) was 106.25 ± 22.14 hr (range 84.11-128.39 hr). Mean absorbed dose for liver, spleen, kidneys, heart, WB and red marrow was 1.0702 ± 0.731, 1.4114 ± 0.462, 1.4232 ± 0.364, 1.4719 ± 0.602, 0.2412 ± 0.0295, 0.1485 ± 0.0213 (mGy/Mbq) respectively by OLINDA EXM and 0.5741 ± 0.333, 0.8096 ± 0.224, 0.7943 ± 0.235, 1.8971 ± 0.713, 0.09619 ± 0.0144 by ORIGIN software. Absorbed radiation dose for tumor is 1.94E+2 by OLINDA EXM software and 1.78E+2 by ORIGIN software. Conclusion: The result of this study demonstrated favourable biodistribution and dosimetry results with indigenously prepared 177Lu-DOTA-Trastuzumab in HER-2 positive breast cancer patients. We observed mean absorbed dose to normal organs within the limits of maximum tolerable dose and also tumor dose was higher than the normal liver dose. Therefore, we concluded that indigenously prepared 177Lu-DOTA-Trastuzumab radioimmunotherapy is feasible and safe treatment option for treating HER-2 positive breast cancer patients.
Other 16: Unprecedented case of prostate neuroendocrine transformation: A case report with a seven year tumor free interval
Vempa Satish
Army
Introduction: This case report focuses on a 65-year-old male patient who experienced a rare neuroendocrine transformation within his prostate following an initial diagnosis of prostate adenocarcinoma. Such transformations pose unique challenges in diagnosis and treatment. As cases like this are seldom reported in the literature, our report underscores the importance of understanding this uncommon phenomenon and the need for further research to clarify its mechanisms and improve clinical management. Materials and Methods: We retrospectively studied a 65-year-old male with neuroendocrine transformation of the prostate, initially diagnosed with adenocarcinoma. Data included biopsy, PSMA PET/CT, DOTANOC PET/CT and PSA monitoring. Tissue samples underwent histopathological analysis, including H&E staining and immunohistochemistry. Treatment involved surgery, radiotherapy, hormonal therapy, and chemotherapy. Ethical guidelines were followed, and informed consent was obtained. Results: The patient's history included a 2014 biopsy report indicating prostatic adenocarcinoma with a Gleason score of 2+4 = 6. He initially presented with lower urinary tract symptoms (LUTS) and received radiation therapy (RT) and hormonal therapy. Impressively, he had a seven-year tumor-free interval following this treatment. In 2021, rising prostate-specific antigen (S.PSA) levels led to further investigation. PSMA PET imaging detected no PSMA lesions within the prostate but revealed PSMA-avid lymph nodes. Subsequently, Abiraterone and Goserelin were administered from September 2021 to March 2023. In 2023, the patient reported low back pain, indicative of clinical progression. A biopsy of a 9th rib lesion confirmed metastatic adenocarcinoma. Enzalutamide therapy was initiated. Immunohistochemistry (IHC) results from the rib lesion biopsy revealed:- Synaptophysin: 3+, Chromogranin: 2+, Ki 67: 65-70%. These findings confirmed neuroendocrine differentiation within the metastatic adenocarcinoma. The clinical progression and emergence of neuroendocrine features underscore the complexity of managing prostate cancer and highlight the need for tailored treatment approaches. Conclusion: In this exceptional case of a 65-year-old male initially diagnosed with prostate adenocarcinoma, the subsequent neuroendocrine transformation posed a complex clinical challenge. DOTANOC PET/CT imaging played a pivotal role in identifying the extent of neuroendocrine features within the prostate. Notably, PSMA scans revealed no uptake in the transformed regions, indicating a potential limitation in PSMA-based imaging for neuroendocrine components. Despite a comprehensive treatment approach that encompassed surgery, hormonal therapy, chemotherapy, and radiotherapy, the disease exhibited relentless progression. This case underscores the rarity of neuroendocrine transformation within prostate cancer and highlights the importance of early detection through imaging modalities like DOTANOC PET/CT. Further research is warranted to better understand the diagnostic and therapeutic implications of neuroendocrine transformation in prostate cancer.
Other 17: Role of fluoride-18 transfer line on 18F-FDG production yield
Raman Kumar, Kiran Dasary, Pardeep Kumar
Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
Introduction: 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) is the most commonly used radiopharmaceutical in clinical molecular imaging. The process of FDG synthesis is under constant development to increase its yield. The transport line material always influences the molar activity of the fluoride-18 [18F]. Materials and Methods: The 18F radioisotopes were produced with our in-house 16.5MeV Cyclotron (PET trace 860, GE Healthcare, USA) by the proton bombardment on the enriched 18O water (from ABX Germany) [18O(p,n)18F] reaction. Fluorinated Polytetrafluoroethylene (PTFE) delivery line (Upchurch Scientific) was used to transfer 18F-fluoride from cyclotron target to the module. We have also accounted the usage of precursor up to its expiry. Around, 9 ± 1 Ci of 18F was transferred through the delivery line to module for the synthesis of 18F-FDG. The standard method was used to calculated yield and later decay corrected. Results: In this study, we have explored the role of PTFE transfer line (18F transport line) on the yield of 18F-FDG. We got yield of around 55 ± 4 % (n = 30) on routine basis but the yield was dropped to 35 ± 15% (n = 3). After evaluating other parameters, we changed the transport line. The yield becomes normal (55 ± 4 %) when the transfer line was changed. These transfer line contains fluorine-19 which may be a contaminant. In routine these tubing was changed during the maintenance of cyclotron but in our experience, it shall be changed after every 100 runs. The other case of dropping yield was observed when we have used a precursor close to its expiry date (one-month prior expiration). It was dropped to 40 ± 5 %. The precursor shall be procured in such a way that it shall be used one month before its expiry. The drop in yield critically matter to the commercial centers. Conclusion: The PTFE transfer line shall be changed after 100 runs or if possible, it shall be replaced with non-fluorinated (PEEK, PP).
Other 18: Effectiveness of lead apron towards effective dose on Lu177 therapy
V. J. Anold, K. K. Kamaleshwara, E. Ramkumar, E. R. Radhakrishna, F. R. Kingsley, M. Sowmiya, R. Ruth, R. V. Rithika, S. Arun Pandiyan, Suvalakshmi
Department of Nuclear Medicine, The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India
Introduction: Radio labeled PSMA-617 (prostate specific membrane antigen) is potential therapeutic target in the treatment of prostate cancer and radiolabeled DOTA-TATE for neuroendocrine tumor (NET). The purpose of the study was to assess the effectiveness of lead apron while administration of 177 Lutetium (177 Lu) radiopharmaceuticals. Materials and Methods: Lead apron and pocket dosimeters. 200mCi of Lutetium-177 PSMA was administered to the patient. While administrating the dose two pocket dosimeter were used to find effectiveness of lead apron. One dosimeter was placed inside the lead apron and another one was placed outside to monitor the effective dose to radiation professional. Both the dosimeter were placed at the chest level. Results: The pocket dosimeter kept outside the lead apron showed 8µSv while that kept inside 2µSv while administering 200mCi of 177Lu PSMA-617. Conclusion: The study concluded that lead apron reduces the effective dose to 1/4th. Hence it proves that using lead apron reduces the effective dose to radiation professional at the time of administration lu177 therapy.
Other 19: Preparation, quality control and bio distribution of Tc99m HYNIC RGD using a commercial kit
Susan Grace Mathew, M. Mufeetha Sherin, Madhusudhanan Ponnusamy, Karthik Balaji
Department of Nuclear Medicine, JIPMER, Pondicherry, India
Introduction: Angiogenesis imaging is an important tool for various malignant and non-malignant diseases. The Arginine – glycine- aspartic acid sequence (RGD) is a tri-peptide antagonist for αvß3 receptors which is expressed in the angiogenic blood vessels and surface of tumor cells. This study is to radiolabel Tc99m HYNIC RGD and observe the normal distribution of αvß3 expression. Materials and Methods: Tc-99m was labeled with HYNIC E [c (RGDfK)] 2 using ready to label kit provided by BRIT, India. As recommended by the manufacturer, about 50 mci of freshly eluted and concentrated (1ml) Tc-99m was added to the vial. The vial was then kept in a water bath for 20 minutes. The preparation was allowed to cool to room temperature. Tc-99m HYNIC RGD has been ready for administration followed by radiochemical purity test (Paper chromatography – MEK and Acetonitrile: water). 15 mci of Tc99m-HYNIC RGD was injected and whole body image was acquired at 60 minutes post injection on 256×1024 matrix size, with patient in supine position. The images were visually analyzed by an expert nuclear medicine physician. Results: The radiolabeling process was convenient and successful and the radiochemical purity of Tc-99m HYNIC E [c (RGDfK)] 2 was found to be 94.3% (Acceptable range falls between 90%-97%). Liver and spleen showed the highest tracer distribution followed by kidneys and urinary bladder which represents the normal route of excretion. Salivary and thyroid also showed mild tracer distribution. Diffuse tracer distribution was seen in the intestine. Conclusion: Radiolabeling of Tc99m with commercially available RGD kit is an easy and convenient process. It has an advantage of being relatively less expensive and easy availability over Ga68-RGD derivatives with optimal imaging characteristics. However acquiring more data will be helpful to obtain the internal radiation dosimetric calculation in the future.
Other 20: Labeling and biodistribution of the novel radiotracer [177Lu] Lu-DOTA-trastuzumab
Dhiya, V. P. Shabeeha Jabeen, Nandini Pandit, Mohini Guleria, Ashok Kumar
Department of Nuclear Medicine, JIPMER, Pondicherry, India
Introduction: Trastuzumab is an FDA approved humanized monoclonal antibody that targets human epidermal growth factor (HER2) receptors which are known to express 20-30% of invasive breast cancer. Patients develop resistance overtime to the drug and some patients cannot tolerate the treatment due to cardiotoxicity. Lutetium -177 is a radio lanthanide with beta emission and a half-life of -6.7 days. Lu-177 Trastuzumab kills the cells by immunologic pathway as well as by the emission of high energy beta particles which causes radiation induced death of the targeted cells. Materials and Methods: Lu-177 was labeled with DOTA conjugated Trastuzumab ready to use cold Kit. The vial containing lyophilized Trastuzumab in a concentration of 5mg was placed in a lead pot of ~10mm wall thickness to attain ambient room temperature. The kit contents were reconstituted in 0.5mL of sterile water and were gently shaken till a clear solution was obtained. 30-60mCi of [177Lu] LuCl3 with high radioactive concentration was added in the cold kit vial and incubated in a water bath at 37°C for 30-45 minutes. The preparation was ready to use after attaining room temperature. Radiopharmaceutical purity test was done using paper chromatography (solvent – 0.01M sodium citrate buffer pH-0.05). Purification using PD10 chromatography column can be used if the radiochemical purity is observed to be less than 95%. Multiple whole body images were taken at 24, 48, 72 and 168 hours post injection of 5 mci of radiotracer to assess the biodistribution and target to background. Images were visually analyzed for quality of the image by an expert nuclear medicine physician. Results: The radiochemical purity of [177Lu] Lu-DOTA-Trastuzumab preparation was found to be >95%. Whole body images at 24, 48, 72 hours showed higher blood pool activity which decreased with increase in time point of acquisition. Homogenous intense tracer uptake is seen in the liver along with the bowel representing the physiological route of tracer excretion. Activity distribution is noted in the mediastinum which clears with time. Delayed images show better blood pool clearance that leads to higher tumor to background ratio. 168 hours image showed overall high target to background ratio. Conclusion: Delayed imaging of Lu177 DOTA Trastuzumab shows better target to background ratio that allows for better visualization of the pathological tracer distribution. Optimal time point of imaging is found to be 7 days post injection. Further delayed images can be acquired but the limitation is the physical decay of Lu177 radioactivity which further affects the overall image quality.
Other 21: Design, in silico studies, synthesis and bio-evaluation of biscyclam-triazole based radioligand: A novel SPECT theranostic agent targeting CXCR4.
Deepika Sharma, Shubhra Chaturvedi, Vinod Prasad Singh, Ankur Kaul, Anil Kumar Mishra
Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
Introduction: C−X−C motif chemokine receptor 4 (CXCR4) is among the most promising targets for therapeutics. Over 67% of the 19.2 million cancer cases diagnosed in 2020 were CXCR4-related, indicating CXCR4 is a crucial target for developing imaging agents and anticancer drugs. Belonging to the G-coupled protein receptor family, Chemokine receptors are not only expressed on malignant tumors but can also be potential theranostic targets for inflammatory diseases and neurodegenerative diseases. The receptor acts as a co-receptor for HIV entry. The novelty of this work is the introduction of triazole linkage using Click Chemistry and further incorporating oxo functionality. The bis cyclam scaffold, known for its CXCR4 affinity and strong coordination with metal ions, was coupled with a triazole moiety to enhance radiolabeling potential. Molecular dynamics simulations and docking studies provided insights into ligand-receptor interactions, aiding the rational design process. This abstract presents a comprehensive overview of developing novel bis cyclam-triazole-based radioligand as a SPECT theranostic agent targeting CXCR4. Materials and Methods: The design and development of the radioligand were initiated through computational studies, utilizing molecular docking software Autodock, Autodock Vina, and Discovery Studio to predict binding interactions. The library of biscyclam-based ligands was prepared, and the ligand with the best G-Score was selected for further development. The synthesis of the novel radioligand was achieved through a multi-step synthetic route, incorporating click chemistry for the triazole linkage and radiolabeling with a suitable radionuclide. The synthesis involved the formations of the following intermediates and the respective final molecule: a) AZIDE-MALONATE (87%) b) CYCLAM-AZIDE (92%) c) ALKYNE-MALONATE (91%) d) CYCLAM-ALKYNE (89%) e) BISCYCLAM-TRIAZOLE (85%). 1H NMR, 13C NMR, and HR-MS characterized the intermediates and the final compound (BISCYCLAM-TRIAZOLE). Column and thin-layer chromatography separation techniques were used to get the desired purified compound. The MTT assay was performed to assess the cellular toxicity on the HEK cell line. No significant toxicity was observed at low micromolar concentrations. The serum stability, blood kinetics, biodistribution, and SPECT imaging studies are in progress. Results: A novel radioligand based on BISCYCLAM and TRIAZOLE moieties was designed, synthesized, and theoretically validated using molecular modeling studies. The G-Score obtained after molecular docking is -9.2, indicating an excellent binding affinity. Receptor ligand interaction studies reveal the presence of Ser263, Phe264, Ile259, Val197, Leu194, Gln200, Tyr256, Ser260, Ile204, Ser46, Phe49, Val198, Leu50, Leu194 and Val196 amino acid residues in the active binding site pocket of this receptor. The final compound, BISCYCLAM-TRIAZOLE, was synthesized with more than 85% yield. Non-toxicity of the radioligand was established by less than 85% HEK-cell kill when incubated with one µM for 48 h and hemolysis data. Future Work: The imaging studies and selectivity studies are underway. Conclusion: Novel Radioligand BISCYCLAM-TRIAZOLE targeting C-X-C Chemokine Receptor 4 was theoretically evaluated. The compound was synthesized successfully. The experimental work confirmed the findings of theoretical studies. Further work will establish its potential application as a theranostic agent for the CXCR4 receptor.
Other 22: Production and supply of kit for the preparation of 99mTc-HYNIC-TOC injection for the diagnosis of neuroendocrine tumors: Our experience over a decade at Board of Radiation and Isotope Technology
Uma Sheri Kumar, Archana Ghodke, Mritunjoy Kundu, Soumen Das, Anupam Mathur, Vijay Kadwad, Usha Pandey
Department of Nuclear Medicine, Radiopharmaceutical Programme, Board of Radiation, and Isotope Technology, Navi Mumbai, Maharashtra, India
Introduction: Overexpression of cell surface somatostatin receptor (SSRs) in well-differentiated neuroendocrine tumors (NETs) are exploited for imaging with radiolabeled somatostatin analogs. Tyrocine-3-Octreotide (TOC), a tailor made octapeptide is specific for somatostatin receptors.99mTc-HYNIC-TOCimaging is used for diagnosis and follow-up of neuroendocrine tumors (NETs). User-friendly, single component kit for the preparation of 99mTc-HYNIC-TOC injection is being routinely produced and supplied by BRIT since 2013 under product code TCK-54. Materials and Methods: HYNIC-TOC was procured from overseas suppliers and SnCl2.2H2O was from Sigma-Aldrich. Final composition of single kit vial in freeze dried form contains 30 µg HYNIC-TOC in 10% ethanol, 10 mg EDDA, 20 mg tricine and 40 µg SnCl2.2H2O in 0.2M phosphate buffer in nitrogen purged WFI, pH 6.2. Since 2013, 35 batches of HYNIC-TOCkits were prepared, batch size ranging from 30 – 60 kit vials and this involved handling of 1 – 2 mg of HYNIC-TOC per batch. Radiolabelling of kit vial involves the addition of maximum 2220MBq/60mCi of 99mTc in the form of NaTcO4 followed by heating in boiling water bath for 20 min. Radiochemical purity (RCP)assessment was carried out as per Radiopharmaceutical Committee (RPC) approved Quality Control (QC) Monograph using ITLC-SG with two solvent systems, MEK and Acetonitrile:Water (1:1 V/V). Other QC parameters such as physicochemical tests (appearance & pH) and biological tests (sterility, apyrogenicity & biodistribution) as per QC monograph has been assessed for every batch. So far, 35 batches corresponding to 1800 vials were formulated. Results: The quality of the ligand is one of the major criteria for the successful kit formulations. HYNIC-TOC in lyophilized form two overseas vendors were identified after careful evaluation. Since, HYNIC-TOC is susceptible to ambient temperature, transport of raw material and the finished productsare carried out in dry ice packaging. This parameterconsiderably influences the pricing of the kit. Our experience over the years showedthat RCP was consistently above 99% (limit >90%) indicating integrity of labelled product. Biodistribution studies in Wistar rats shows >90% clearance from kidney at 4h post injection. All other physicochemical and biological tests complied with QC monograph. These kits were found to be stable up tonine months when stored at –20oC, however, considering logistics and other factors, expiry date of the kit is 6 months from the date of production. Conclusion: Over the years, around 1450 kit vials (maximum 4350 diagnosis) were supplied to Nuclear Medicine Centers throughout India with utmost customer satisfaction. Production of kit formulations at cGMP, ISO 9001:2015 & ISO 13485:2016 certified facility at BRIT, Navi Mumbai by well-trained scientists, strict adherence to SOPs resulted in zero batch failure till date.
Other 23: Nuclear medicine in postoperative biliary and genitourinary diagnoses
Deepak Prabataram Kalbi, Deepak Kalbi, Aspan Shokrekhuda, Kwang Chun
Montefiore Medical Center, Bronx, NY, USA
Background: This article emphasizes the importance of nuclear medicine studies after surgery, specifically for biliary and genitourinary issues. After surgery, it's crucial to differentiate between normal healing and complications like fluid leaks. Nuclear medicine scans help clarify these situations. Methods: We highlight the value of nuclear medicine tests like hepatobiliary scintigraphy and renal scans in solving post-surgery diagnostic puzzles. These tests are especially useful when there's suspicion of bile or urine leaks alongside visible fluid collections. We present a series of cases illustrating how nuclear medicine scans aided in diagnosing biliary leaks, unusual bile ducts, gallbladder remnants, and urinary complications after genitourinary surgery. Results: In the first case, a patient with post-cholecystectomy pain had a bile leak, confirmed by biliary scintigraphy. Another case revealed an accessory bile duct of Luschka using the same method. In the third case, biliary scintigraphy identified a gallbladder remnant. Additionally, we confirmed a ureterocolic fistula post-ureteric stent placement with a Tc99m-MAG3 renal scan, showing tracer in the colon. Post-renal transplant urinary leaks were diagnosed using Tc99m-DTPA due to Tc99m-MAG3 unavailability. Conclusion: Functional nuclear medicine imaging is vital in diagnosing complex post-surgery biliary and genitourinary issues. This article showcases the usefulness of these scans in resolving diagnostic challenges, leading to precise diagnoses and better patient outcomes.
Other 24: Evaluation of personnel radiation exposure during manual PET-CT guided biopsies
Priya Sharma, Gurudas Singh, Mansha Vohra, Praveen, Tarun Kumar Jain, Karan Singh Peepre
Department of Nuclear Medicine, Mahatma Gandhi University of Medical Sciences and Technology, Jaipur, Rajasthan, India
Introduction: The present study aimed to evaluate the radiation burden to personnel performing manual positron emission tomography/computed tomography (PET/CT) guided biopsies and to staff assisting the procedure in a PET/CT facility. Materials and Methods: This prospective study was conducted over a period of 8 months (from march 2022 to October 2022). A total of 60 patients underwent manual PET/CT-guided biopsy from a tracer avid site after intravenous radiotracer injection. The whole-body dose to the physician and assisting staff was measured with calibrated pocket dosimeters and exposure rates from patient were measured with calibrated ionization-based survey meter during the procedure. Results: A total of 60 patients (males – 42, females – 18) with a mean age of 58.2 ± 15 years (range 23 - 73 years) were included in the study. Out of 60 biopsy procedures, 22 were bone biopsies, 15 were from abdomen/pelvic region, 16 were lung biopsies, 5 were breast and 2 were oral cavity biopsies. Among 60 patients, the injected radioactivity was different due to some patients were scheduled for intervention on same of whole-body PET-CT imaging. The mean time elapsed between injection and procedure was 151 ± 80.1 min. The mean exposure rates measured at the surface of abdomen and 1 meter distance from the patient was 35.64 ± 23.4μSv/h and 3.67 ± 2.9μSv/h, respectively. The mean time taken to perform the procedure was 15 ± 9 min. The mean whole-body exposure to the physician and assistant staff was found to be 1.06 ± 0.56μSv and 1.23 ± 0.52μSv respectively. The whole-body exposure rates for physician in soft tissue & bone biopsies were 0.88μSv and 1.25μSv respectively. While assisting staff exposure rates were 1.18μSv and 1.25μSv for soft tissue & bone biopsies respectively. Conclusion: We concluded that during PET-CT guided biopsies, exposure rates from the procedure to the physician and assisting staff are within the safer limits specified by regulatory authority. However, in present study, the secondary staff is getting relatively more exposure than the primary physician because pre and post procedural monitoring is done by assisting staff. So, rotation of the secondary staff may be more convenient step in order to minimize the exposure.
Other 25: Synthesis, characterization and radiolabelling of bioactive peptide-based Schiff base as potential chelating agent in nuclear medicine
Presenjit, Shubhra Chaturvedi, Divya, Ritika, Sunil Pal, Kaman Singh, A. K. Mishra
Radiological Nuclear and Imaging Sciences, INMAS, DRDO, Delhi, India
Introduction: Radiopharmaceuticals are extremely effective diagnostic instruments for assessing a wide range of medical disorders. These medications have radioactive isotope labels that are used to provide images of target locations through drug administration. Peptides and Schiff bases, which are biologically active molecules, function as targeting vectors for radiopharmaceuticals utilizing 99mTc. The CGKRK-SB (Cysteine-glycine-lysine-arginine-lysine-Schiff base) compounds are invaluable assets in medicinal realm. Their extraordinary properties, including cell penetration, targeted tumor therapy, angiogenesis inhibition, and therapeutic protein delivery, make them pioneers in cutting-edge research. Materials and Methods: This study encompasses the synthesis, characterization, and radiolabeling of CGKRK-based Schiff base complexes incorporating nonradioactive rhenium, 99mTc or 188Re. The peptide was synthesized using a solid-phase synthesis approach, employing N-(9-fluorenyl)methoxycarbonyl (Fmoc)-based chemistry and Fmoc-L-amino acid building blocks, conducted under a nitrogen atmosphere at room temperature. Subsequently, another amino acid was utilized to transform it into an aldehydic amino acid, essential for the formation of the Schiff base. After that, the encapsulation of 99mTc within the CGKRK-SB ligand was carried out, with optimization of conditions such as pH, time, and the concentration of the reducing agent to achieve the highest radiolabeling efficiency. These complexes were analysed through spectroscopic methods like XRD, IR, flash chromatography, Mass spectroscopy, and CD techniques. In vitro studies, including haemolysis and MTT assays, were conducted to assess blood biocompatibility and cell cytotoxicity. Furthermore, in vivo experiments and molecular imaging will be performed to validate the synthesized Schiff base complexes. Results: The pentapeptide-based Schiff base complexes were effectively synthesized and comprehensively characterized using a range of spectroscopic techniques, including XRD, IR, flash chromatography, Mass spectroscopy, and CD analyses. An outstanding efficiency of (>92%) during the radiolabeling with 99mTc confirmed the successful loading of the radiotracer. Analysis of the CGKRK-SB complexes using spectroscopic data verified successful complexation and revealed the existence of two complexes in syn and anti-conformations. Furthermore, cell viability assays and hemolysis tests conclusively indicated that the CGKRK-SB complexes formed exhibited no notable cytotoxic effects on the tested cell lines and demonstrated excellent blood biocompatibility. Conclusion: The emergence of CGKRK-SB, a pentapeptide-based Schiff base ligand, highlights its considerable potential as a valuable chelating agent for both imaging and therapeutic roles within the realm of radiopharmaceuticals. This work has the potential to significantly assist patients through promoting early disease detection and personalised therapy approaches, which will improve healthcare outcomes and general wellbeing.
Other 26: To assess response to empirical radioiodine therapy in patients with papillary thyroid carcinoma
Einsteinpaul, Julie Hephzibah
Department of Nuclear Medicine, Christian Medical College, Vellore, Tamil Nadu, India
Introduction: Papillary thyroid carcinoma is the predominant form of thyroid cancer, accounting for 80 to 85% of all thyroid cancer cases, which require radioiodine for disease-free survival. For differentiated thyroid cancer (DTC) patients with thyroglobulin (Tg) elevation and negative iodine scintigraphy after thyroidectomy, thyroid-stimulating hormone (TSH) suppression therapy, and empirical RAI therapy may be considered. Materials and Methods: A total of 100 patients who underwent empirical therapy from Jan 2008 to Dec 2019, which includes a total of 51 men and 49 women with ages ranging from 16 to 75 years are included in the study. Follow-up period ranging from a minimum of 6 months to a maximum up to 12 years. Histological types included were classical, follicular, oncocytic, tall cell and microcarcinoma. The level of serum thyroglobulin was assessed during follow-up. Results: Of the 100 patients, who underwent empirical radioiodine ablation, 4 patients had 3 empirical ablations, 23 patients had 2 ablations and 73 patients had 1 empirical ablations. 38 patients had regression of disease status in the form of decreasing trend of serum thyroglobulin during their follow-up. Fifty-two patients had progression post empirical therapy during follow-up up and out of these 8 had local recurrence and managed surgically while other 15 patients are started on TKI while others will be planned for TKI depending upon their clinical and radiological status. 8 patients had stable disease and 2 patients lost for follow up after the empirical ablation. Conclusion: Empirical therapy seems to be a reasonable and a feasible option in treating patients with TENIS as there are limited treatment options available. In our study, we found that 46% of the patients showed significant regression of disease with no limitation on the Quality of life. The other options such as TKI's or other upcoming therapy options like DOTA and FAPI therapy are expensive and we need validation of this treatment.
Other 27: Development and validation of a MeVisLab network to display PET/CT images and view image acquisition and processing related information
Jyoti Yadav, Anil Kumar Pandey, Madhavi Tripathi, Jagrati Chaudhary
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
Introduction: The PET and CT images are usually reviewed on Image Processing terminals provided by the vendor. In the busy nuclear medicine facility which is dedicated for both patient care and academics, the limited number of terminals (because of cost and space requirements) are primarily used for patient care activities. Now a days, Laptops are available with post graduate students that can be effectively utilized for the research purpose. In this study we have utilised an open source software called MeVisLab that can be installed on Laptop and designed a MeVisLab (ML) network to display the PET/CT image and also reviewing the information stored in the DICOM file. Materials and Methods: MeVisLab has several modules in which each module has input and output port. Output of one module can be connected to input of another module through graphical user interface. This makes it user friendly and produces result reasonably fast. In order to develop the MeVisLab network to display PET/CT images and view image acquisition and processing related information, the following modules: Direct Dicom Import, Dicom Rescale, Dicom tree item model and view2D were combined as shown Figure 1, Middle. Modules used in our network are briefly explained as follows:
DirectDicomImport: This module reads the Dicom files. It automatically reads the image data and its attributes and load into memory
DicomRescale:The module allows for a rescaling of Dicom data to a user-defined intercept, slope, and data type
Dicom tree item model: This module allows to display the image acquisition and processing related information stored in Dicom file
View2D; The module provides a viewer to display two-dimensional image with the possibility to scroll through the slices in 3D.
Results: The developed network and its results is shown in Figure 1. The user can click the button “DirectDicomImport” to select the patient DICOM study to be explored. A click on “View2D” will display the image slice [Figure 1 right shows a CT slice]. A click on “Dicom tree item model” displays the informations available in the DICOM file. The CT image displayed in Hounsfield Unit (HU) on Laptop have been compared with the same image displayed on the vendor terminal and found to be same. Conclusion: The designed a MeVisLab (ML) network can be used to display the PET/CT image and also reviewing the information stored in the DICOM file on Laptop (independent of vendor terminal).
Other 28: Standardization of image quality parameter for compression of Tc-99m Bone scan image using WebP image file format
Jyoti Yadav, Jagrati Chaudhary, Anil Kumar Pandey, Jyoti Yadav, Rakesh Kumar
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
Introduction: WebP is an image file format that provides superior lossless and lossy compression for images on the web. This format is developed by Google developers; and it provides lossless image that are 26% smaller in size compared to PNGs; and lossy image 25-34% smaller than comparable JPEG images at equivalent SSIM quality index. In this study, we have standardized the image quality parameter for the compression of Tc-99m MDP bone scan image. Materials and Methods: One hundred and six Tc-99m MDP Bone scan images acquired on SymbiaT6 SPECT/CT gamma camera system equipped with low energy high resolution collimators. These images were exported in DICOM format, and then converted in PNG format. The PNG images were compressed at different image quality (IQ) parameters namely 10, 20, 30, 40, 50,60, 70, 80, 90, and 100. The quality of compressed image was compared visually with its input PNG image. Nuclear Medicine Physicians had evaluated all 106 images of Tc-99m MDP bone scan images and labelled as acceptable and unacceptable. Results: As per NM physician, all 106 compressed Tc-99m MDP Bone scan images at image quality parameters: 70, 80, 90, & 100 looks identical to the original images. The summary statistics of the percentage compression achieved at different image quality parameters is given Table 1. The median compression achieved at image quality (IQ = 70) was 84.62% with no loss of image quality. Although the compressed image at image quality 80,90 and 100 were also similar to its input image; however, the percentage compression achieved was smaller than 84.62% (Obtained with image quality = 70). Conclusion: The standardized value of the image quality parameter for the compression of Tc-99m-MDP-bone scan image was found to be 70 that provides 84.62% compression.

| IQ parameters | Summary statistics | |||||
|---|---|---|---|---|---|---|
| Minimum | 1st quartile | Median | Mean | 3rd quartile | Maximum | |
| 60 | 81.12 | 85.40 | 87.23 | 86.94 | 88.32 | 91.72 |
| 70 | 78.49 | 82.90 | 84.62 | 84.42 | 85.92 | 89.40 |
| 80 | 71.25 | 76.51 | 78.18 | 78.02 | 79.57 | 83.35 |
| 90 | 54.93 | 61.37 | 63.34 | 63.03 | 65.14 | 69.54 |
| 100 | 13.36 | 25.74 | 27.53 | 26.99 | 29.20 | 36.82 |
IQ: Image quality
Other 29: Comparative performance of 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT for the detection of metastatic prostate cancer
Monika Hooda, M. Hooda, B. Singh, H. Singh, S. Prashar, K. Kaur, S. K. Singh, R. Mavuduru, A. P. Sharma, N. Kakkar
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: Gallium-68 - prostate specific membrane antigen (68Ga-PSMA)-PET is the ‘standard-of-care’ molecular based imaging for initial staging and planning for 177Lu-PSMA based ligand therapy in metastatic prostate cancer (PCa). The treatment response monitoring following multiple doses of 177Lu-PSMA require periodic 68Ga-PSMA PET procedures. The later poses constraints on Nuclear Medicine centres not having access to PET and 68Ge/68Ga technologies. The present study was designed to investigate if 99mTc-PSMA is comparable to 68Ga-PSMA in the management of advanced stage PCa patients undergoing indigenously produced 177Lu-PSMA made available at an affordable cost. Materials and Methods: Sixty-one (mean age 67 ± 7.82 years) male patients with metastatic prostate cancer underwent 99mTc PSMA whole-body scan after intravenous tracer injection (mean activity = 12.82 ± 1.15 mCi). Anterior and posterior whole-body images (matrix size = 256×1024; scan speed = 12cm/min) were acquired at 2.0-h and 4.0-h using a dual-headed gamma camera. Additional SPECT/CT images (matrix size 128×128 and zoom factor 1.5) were acquired at 3.0-h for the involved sites, when planar images did not clearly identify the metastatic sites. All the patients also underwent whole-body 68Ga-PSMA PET/CT. The two imaging procedures were done within one week and no other intervention was done during the week. The reconstructed images of the two techniques were analysed for the detection of the tracer avid lesions. Results: The radiopharmaceutical purity (RCP) of the resultant 99mTc-PSMA product was > 90.0%. The mean PSA levels were found out to be 164.12 ± 461.89 ng/ml. Tracer uptake was seen in 59/61 (98.3%) patients both on 68Ga-PSMA PET/CT and 99mTc-PSMA SPECT/CT. In 1 of the remaining 2 patients, the biopsy from the site of the increased 68Ga-PSMA PET uptake confirmed it as benign prostatic hyperplasia. In the 2nd patient, 68Ga-PSMA showed no post-surgery (prostatectomy) tracer uptake in the prostate bed, but uptake was noted in the sub-centimetric 3 (right external iliac-1 and preaortic-1 and paraaortic-1) lymph nodes. In both these 2/61 patients, no tracer uptake was noted on 99mTc-PSMA imaging. 68Ga-PSMA detected 341 pelvic lesions whereas, 99mTc-PSMA detected 301 (88.2%) lesions. On the other hand, 68Ga-PSMA detected 237 extra pelvic distant metastatic lesions and 99mTc-PSMA detected 208 (87.8%) extra pelvic lesions. This comparative analysis demonstrated that 68Ga-PSMA detected a total of 578 lesions (9.5 lesions/patient) whereas, 99mTc-PSMA detected a total of 509 lesions (8.3 lesions/patient). Thus, 99mTc-PSMA provided an overall sensitivity of higher than 88.0% in comparison with 68Ga-PSMA PET/CT. The findings of the two imaging modalities were used for disease staging using the latest TNM classification. The UCSF-CAPRA for 68Ga-PSMA and 99mTc-PSMA were estimated to be 6.60 ± 2.53 and 6.56 ± 2.56 (n = 61) respectively. Conclusion: 99mTc-PSMA is nearly an equivalent (detection rate = 88.0%) imaging modality to 68Ga-PSMA for the detection of metastatic lesions in PCa. The impact of the marginal diagnostic inferiority of 99mTc-PSMA in not picking up a small fraction of metastatic lesions (possibly lesions of size below the resolution of SPECT) on the overall management of these patients needs to be investigated.
Other 30: Evaluation of GFR estimation techniques in obstructive uropathy: 99mTc-DTPA plasma sample method, gates method and serum creatinine based eGFR methods
Jeevan Shrestha, J. Shrestha, M. L. Narayan, P. Palanivel, R. Subramani, S. Sanisetty, A. Mittal1
Departments of Nuclear Medicine and 1Urology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
Introduction: Glomerular filtration rate(GFR) is an important indicator of renal function. 99mTc-DTPA camera based Gates’ method, plasma sample method and eGFR equations based on serum creatinine can all be used to measure GFR. In clinical research, Plasma sample method(PSM) has emerged as the gold standard for more accurate estimation of GFR. Obstructive uropathy(OU) is disorder of urinary tract that occurs due to obstructed urine flow from the kidney to the bladder. Renal stone disease(RSD) or pelviureteric junction obstruction(PUJO), are the common causes of urinary tract obstruction in adults, which can result in reduction of GFR and renal plasma flow. Many of currently available methods overestimate the GFR, including Gates’ method in hydronephrotic kidney with obstructive uropathy. The goal of the study was to compare the estimated GFR using 99mTc-DTPA plasma sample method(two sample method, PSM) as a reference standard, with gamma camera based Gates’ method and S. creatinine based estimated GFR(eGFR) methods in patients with obstructive uropathy(RSD or PUJO). Materials and Methods: This prospective observational study was carried out in Department of Nuclear Medicine, AIIMS Rishikesh, Uttarakhand. A total of 105 adult patients with obstructive renal disease (62 males & 43 females) were enrolled for 99m-DTPA renal scintigraphy. Out of 210 kidney units(KU) analysed in 105 patients, RSD was noted in 80/210 KU & PUJO was seen in 47/210 KU. Patients were injected 4-4.5mCi of 99mTc-DTPA and dynamic renal scan was performed immediately after injection using gamma camera. For PSM, blood samples were taken at 60 and 180 minutes from the arm contralateral to the site of injection. After 24 hours, a total volume of 1 ml of plasma from each sample and standards were counted in an automatic gamma counter for 1 min. Serum creatinine level was estimated within 72 hours before or after renal scintigraphy. Results: The median age for the population was 36 years (mean age 38 ± 13.7 years). The mean serum creatinine level was 0.84 ± 0.30 mg/dl. In this population, the Gates method had a good correlation (r = 0.842, p <0.001) with PSM. The correlation between PSM with other eGFR estimation methods like CG, MDRD and CKD-EPI 2021 were 0.560, 0.589 and 0.706 (p < 0.001) respectively. Bland Altman plot analysis of mean differences in GFR (at 95% CI) for Gates vs PSM was 11.6 ml/min/1.73m2 [limit of agreement: -16.1 to 39.3], for CG vs PSM 36 ml/min/1.73m2 [limit of agreement: -23.8 to 95.8], for MDRD vs PSM was 35.3 ml/min/1. 73m2 [limit of agreement -25.2 to 95.8] and for CKD-EPI2021 vs PSM was 38.3 ml/min/1.73m2 [limit of agreement was 4.9 to 71.7] were obtained. The accuracy (P30) of Gates method of GFR estimation was 79.05%, when compared with PSM method of GFR estimation. However, P30 for CG, MDRD and CKD-EPI 2021 was 26.67%, 36.19% and 12.38% respectively. In our study, there was a good correlation noted between estimated GFR by Plasma sample method(PSM) and Gates’ method in patients with OU with better accuracy than the eGFR methods of GFR estimation. The PSM of GFR estimation is more accurate for estimating global GFR in OU especially in patients with bilateral PUJO, RSD & renal impairment. To conclude, plasma sample method(PSM) of GFR estimation is reproducible in this subgroup of patients and can be recommended as standard method for more accurate estimation of GFR.
| Methods to calculate GFR | Mean ± SD (ml/min/1.73m2) |
|---|---|
| Plasma Sample Method | 68.0 ± 14.9 |
| Normalised Gates GFR | 79.5 ±24.2 |
| CKD-EPI 2021 | 106.3 ±23.9 |
| CG method | 104.0 ±36.2 |
| MDRD method | 103.3 ±37.1 |
Other 31: Radioactive simulations and validation studies to optimize parameters for the cyclotron-based production of scandium-44 using 44Ca(p,n)44Sc reaction
Kirti Dhingra, Sukhvir Singha, Kirti Dhingra, Nitin Kumara, Puja P. Hazaria
Advanced Radioisotope Production Center, Institute of Nuclear Medicine and Allied Sciences, Delhi, India
Introduction: Improvements in predictive tools like Monte Carlo simulations evolved the use of simulations for radionuclide yield calculations with respect to optimized beam parameters (proton energy, current, time of irradiation) and could accurately predict the yield of several contaminants produced during irradiation, which can help curtail the cost of enriched target materials (by optimizing target thickness, material, and geometry) and effective resource utilization. 44Scandium (half-life = 3.97 h) has favorable nuclear properties for diagnosis using Positron Emission Tomography, in conjunction with β- emitter 47Sc, making the combination of a suitable pair of radionuclides for “theranostics” in Nuclear Medicine. For this purpose, an accurate knowledge of the cross sections is mandatory. Therefore, in the present study, GEANT4 Monte Carlo simulations were utilized to model the solid Targetry of INMAS-PETtrace (16.5 MeV) medical cyclotron. Radioactive Simulations and Validation Studies were carried out to optimize irradiation parameters and the cross-section measurement of the nuclear reaction 44Ca(p,n)44Sc for efficient production of high-purity 44Sc radioisotope. Materials and Methods: Geant4 v11.1.1 Monte Carlo Codes were utilized to perform simulations using the Linux (Ubuntu v 22.04.2LTS) operating System. Thin target simulations were performed with the geometry of a 10 μm thick cylinder and 1 cm diameter to verify the Geant4 inelastic proton interactions, with a uniform flat proton beam incident on the circular surface. The energy of the protons was varied between 1 MeV and 20 MeV in 1 MeV increments, and 106 primary events were generated. Energy-dependent Cross-section of the reaction 44Ca(p, n)44Sc for the simulated MC model has been calculated theoretically by knowing the value of the number of protons per unit surface hitting the target (Ф), radionuclides created through the inelastic proton interactions in the target (reactive volume) and atomic density in the target from energy 2 MeV to 20 MeV of target thickness 10µm. The cross-sections calculated in our study from the results of the Geant4 simulation of thin targets were compared to the TENDL-2019 library and recommended cross-sections from the IAEA Medical Isotope Browser (MIB) tool for validation. The experimental results were also compared using EXFOR library, which contains numerous measurements of the cross-sections of proton-induced nuclear reaction on calcium-44. Results: The comparison of the TENDL-2019 cross-sections, IAEA-MIB, and the cross-sections computed from the result of the Geant4 simulation of thin targets are found to be in concordance. It is observed from the data that the cross-section of 44Ca(p, n)44Sc nuclear reaction has a broad maximum of ~600mb in the proton energy range 10-13MeV which can be used for optimum production yield of 44Sc. Conclusion: Geant4 MC model of solid targetry system and simulations of interactions of protons with target material has been validated successfully for optimization of various parameters for 44Sc production using medium energy cyclotron. This could serve as a cost-effective and radiologically safe theoretical tool to study the production yield of many other potential theranostic radioisotopes in the field of nuclear medicine.
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Other 32: Biodistribution of 99mTc MDM (DTPA-bis-MET) in BIRADS IV & V breast lesions: An exploratory study
Meena Negi, Manishi L. Narayan, Vandana Kumar Dhingra, Vivek Kumar Saini, Bina Ravi, Puja P. Hazari1, Anil K. Mishra1
Department of Nuclear Medicine, AIIMS, Rishikesh, Uttarakhand, 1Department of Nuclear Medicine, INMAS (DRDO), Delhi, India
Introduction: Radionuclide-based SPECT and PET tracers have been used in early diagnosis of breast cancer. The C-11 methionine is a PET tracer but it is expensive and not widely available in many centres. SPECT-based tracer 99mTc- MDM (DTPA-bis-methionine) has shown promising results with brain tumor imaging. The uptake of 99mTc MDM is facilitated by the upregulation of amino acid transporters and transported in tumor cell by LAT1 transporter. It is readily available at low cost and could possibly be used as an effective method for the detection of malignant breast lesions. But there is limited data in the literature on MDM imaging in breast cancer. Aim: To explore the possibility of indigenously prepared 99mTc-MDM for early diagnosis of breast cancer. Also, to assess the tumor uptake ratio and biodistribution of 99mTc-MDM in patients with BIRADS IV &V breast lesions suspected of malignancy (MMG). Materials and Methods: Methodology: Histopathological proven case of breast cancer (n = 37) with BIRADS-V lesions and patients with radiologically indeterminant (BIRADS IV) & benign breast lesions, were prospectively enrolled for 99mTc-MDM scintimammography. For 99mTc-MDM labeling,15-20mCi Sodium pertechnetate was added in a vial for a single patient to make the volume to 1.5ml with 0.9% sodium chloride and equal volume of air was withdrawn from the vial & mixed well. Thereafter vial was kept for incubation for 15-20 minutes. After incubation, 99mTc-MDM was filtered through Millipore filter 0.22µm before administration. Approx., 15-20mCi of 99mTc-MDM was injected intravenously to the patients under gamma camera. Immediate flow images, blood pool, spot images (Anterior/Posterior &Lateral Prone) &whole-body images were acquired at 10,60 and 180 minutes. Regional SPECT/CT of Thorax was done (if needed). Radiopharmaceutical labeling was assessed qualitatively and quantitatively. Images were correlated with other imaging like Mammography, Ultrasound, MRI, & HPE. For all patients, the uptake with the mean & SD were calculated at 10min,1hr and 3hr. Results: Total 37patients with BIRADS-IV &V breast lesions were available for evaluation. Total 36/37patients had BIRADS-V lesions and all BIRADS-V breast lesions showed significant MDM uptake at 10min,1hr&3hrs, with mean Tu:Bkg ratio of (2.606 ± 0.601),(2.941 ± .079) & (3.04 ± 1.114) respectively in anterior view and (1.89 ± 0.578),(1.95 ± 0.717) & (2.059 ± 0.728) respectively on Prone Lateral images. Only 1 out of 37 patients had BIRADS-IV lesion which did not show significant 99mTcMDM uptake till 3hrs of imaging. Biodistribution of this tracer and its labelling efficiency on the scans was found to be satisfactory in all patients. Physiological tracer uptake was seen in kidneys, gall bladder, liver and bowel. Conclusion: In our study, there was significant 99mTc-MDM uptake & retention seen in all malignant lesions but no uptake was noted in pathological proven benign breast lesion. Current study indicate that 99mTc-MDM Imaging is a feasible alternative to PET and could possibly be used for breast cancer imaging. However, its role in correctly identifying the malignancy in radiologically indeterminant lesions (i.e. BIRADS-IV)needs to be further assessed in a larger population.
Other 33: Appropriation of timing for administration of furosemide and evaluation of image quality after administration of furosemide in 99mTc-MDP Bone Scintigraphy
Praveen Gururani, Mr Prabhat, Prof. Satyawati Deswal
AIIMS, JODHPUR
Introduction: Radionuclide bone scintigraphy is one of the most frequently performed investigations in nuclear medicine. The imaging is generally performed 2–4 hours post intravenous administration of 500–1110 MBq or 13-30 mCi of 99mTc-MDP. Binding occurs by chemisorption in hydroxyapatite mineral component of osseous matrix. Approximately 50% of the dose is localized to the bone, remaining excreted by kidneys. Although peak bone uptake occurs approximately 1 hour after injection, images are usually taken at approximately 3 hours to balance the target to background ratios. For reducing this delay time, a diuretic (such as furosemide) can be used. The role of Lasix in bone scintigraphy is to increase renal filtration of 99mTc-MDP, which would result in reduced tissue background activity and improve bone contrast. The aim of our study was to determine appropriate time of furosemide administration and evaluate the image quality after its administration Materials and Methods: A prospective study was conducted between January-2021 to August-2021 at Department of Nuclear Medicine, Dr. RMLIMS, Lucknow. Image acquisition of 41 subjects was analyzed prospectively for the patients who underwent bone scintigraphy in our department. Patients catheterized for urination, suffering from pelvic pathophysiologies such as Ca Prostate patients suffering from hypercalcemia, pregnant females, patients below 20 years of age & non consenting patients were excluded. To find out appropriate timing of furosemide injection, patients were injected with 99mTc-MDP and were divided into 4 groups with furosemide administration at (F-20), (F-0), (F+20) & (F+40) protocol. Images were acquired post 90 minutes and 150 minutes of 99mTc-MDP administration. Images were independently analyzed by two blinded Nuclear Medicine Physicians. Abdominal area had Lumbar vertebra as target and proximal abdominal tissue as background for count analysis and calculation of TTBR. In, pelvic joint area, head of femur was chosen as target and superiolateral adjacent tissue as background tissue. ROIs were drawn over target and background areas in abdomen and pelvis for quantitative assessment and statistical analysis. Results: On comparison, the TTBR was higher in group-IV patients in both the sets of acquisition at abdomen and pelvis, but there was no significant difference in TTBR in between group-I, group-II and group-III patients between two set of acquisitions. Also the computed TTBR in patients imaged at 90 minutes was almost equivalent to TTBR in patients imaged at 150 minutes post IV administration of 99mTc-MDP. Conclusion: The appropriate timing of furosemide administration is 40 minutes after IV injection of 99mTc-MDP. Additionally, patients for bone scintigraphy can be imaged earlier (at 1.5 hours) than the conventional imaging time (at 3 hours) as almost equivalent target to background ratios were achieved in ninety minute imaging. This reduction of clearance period can help in imaging more number of patients for bone scintigraphy in a busy NM department.
Other 34: Simultaneous blood glucose parameters in type 2 diabetic patients with delayed gastric emptying
Tanisha Gupta, Rajesh Kumar, Sameer K. Taywade
Department of Nuclear Medicine, AIIMS, Jodhpur, Rajasthan, India
Introduction: Gastroparesis is defined as abnormally delayed gastric emptying with no evidence of mechanical obstruction. Diabetic gastroparesis can have adverse consequences including poor glycemic control with difficult to control and fluctuating blood glucose levels. In this study, we have evaluated the relationship between delay in gastric emptying and simultaneous blood glucose parameters. Materials and Methods: It was a prospective study conducted in 20 type 2 diabetics diagnosed for at least 1 year. The patients underwent gastric emptying scintigraphy using radioactive idli meal (Caloric content = 282kcal) and continuous glucose monitoring (the system measure blood glucose levels at every 5 minute interval) simultaneously. ROI was placed over anterior and posterior stomach on planar images for total stomach. The parameters of percentage emptying at half hour intervals till 4 hours, linear fit t1/2 and linear fit slope were used for gastric emptying and absolute glucose levels, time to peak, area under curve, peak glucose and mean blood glucose levels for continuous glucose monitoring were used for analysis. According to the gastric emptying results, 9 patients had delayed emptying (Mean age = 54.33 ± 6.98 years, M:F = 6:3). The correlation between the above mentioned parameters was done using Pearson and Spearman correlation coefficient for normally and non normally distributed data respectively. As the sample size for the study was small, P value of <0.05 was considered significant, and P value between 0.05 and 0.1 was considered as trend towards significance. Results: At P value of <0.05, statistically significant moderate positive correlation was noted for gastric emptying percentage at 4 hours and time to peak and AUC 2 hour. Gastric emptying percentage at 3 hours and 3 hour 30 min show moderate positive correlation with peak blood glucose level and AUC at 2 hours. At P value of <0.1, moderate positive correlation was noted between AUC 1hour and gastric emptying at 3 hour, 3 hour 30 min, 4 hour, AUC 2hour and gastric emptying at 3 hour, 3 hour 30 min, 4 hour and linear fit slope, AUC 3 hour and gastric emptying percentage at 3 hour and 3 hour 30 minutes. AUC 1 and 2 hour showed moderate negative correlation with linear fit t1/2. Conclusion: The above results indicate that delay in gastric emptying can affect the blood glucose curve and it can cause fewer excursions of blood glucose with more prolonged rise of postprandial blood glucose levels. Gastroparesis, per se, as a complication of diabetes, can cause poor control of diabetes. In those patients, there is a need either to treat gastroparesis or to change the timings of medications to achieve optimum action. Thus, simultaneous interpretation of continuous glucose monitoring and gastric emptying may help in the individualized management of diabetic patients.
Other 35: Past present and future prospects of small animal imaging modalities
Arushri Srivastava, Mrs. Sushama Awasare
AIIMS Jodhpur
Introduction: Translational research is changing the practice of modern medicine and the way in which health problems are approached and solved. The use of small-animal models in basic and preclinical sciences is a major keystone for these kinds of research and development strategies, representing a bridge between discoveries at the molecular level and clinical implementation in diagnostics and/or therapeutics. The development of high-resolution in vivo imaging technologies provides a unique opportunity for studying disease in real time, in a quantitative way, at the molecular level, along with the ability to repeatedly and non-invasively monitor disease progression or response to treatment. This abstract reviews the literatures available on the importance of pre-clinical research and the related modalities for their importance in the field of nuclear medicine. Materials and methods: This is a scoping review of the literatures available which was done at the Radiation Medicine Center, Mumbai using Rayyan software. Websites/Browsers: Pubmed, tech.snmjournals, researchgate, Wikipedia Keywords: “pre-clinical” “small-animal imaging” “molecular imaging” “small animal imaging advancements” “in-vivo small imaging” Results: The implementation of preclinical imaging over the past 20 years has allowed morphological and functional explorations at different scales (molecules, cells, tissues, organs, systems, whole body) which explain its expanding use in research. Nuclear medicine encompasses 2 main technologies “single-photon emission computed tomography (SPECT) and positron emission tomography (PET)”, which have driven the field of molecular nuclear medicine forward and the correlation of which to preclinical imaging and its modalities hold immense importance. Animals are necessary for biomedical research mainly because of their short life cycle and genetic similarities to humans. Extensive data from animal studies are needed for a drug's dose, its bio-distribution and route of administration, effectiveness and toxicity. Imaging modalities that are non-invasive and in vivo are especially important to study animal models. These imaging systems can be categorized into primarily morphological/anatomical and primarily molecular imaging techniques, which if specifically designed for the small animals with improved resolution, sensitivity and field of view result in better investigative abilities to longitudinally study various experimental models of human disease in small animals. These may include micro computed tomography, Micro magnetic resonance tomography, micro single-photon-emission tomography, Micro positron-emission tomography, ultrasound, optical imaging digital angiography and others. Various advancements in the in-vivo imaging, such as the “all-in-one” approach to multimodal imaging such as bi and tri modality systems (U-SPECT I and U-SPECT II) can provide a wealth of information, with improved imaging time and increased output for research and development. Conclusion: The continued refinement and increased availability of small animal imaging modalities can lead to rapid progress in the ways that tumour biology can be visualized non-invasively. There can be a significant increase in the overall utility of mouse tumour models by using small animal imaging approaches, which in turn would result in improved clinical practices.
Other 36: Addressing radiation safety challenges in security screening: distinguishing active patent travelers from illicit radioactive material transport
S. Pathak, B. Shimja, P. Tandon, P. K. Dash Sharma
Atomic Energy Regulatory Board, Mumbai, Maharashtra, India
Introduction: In Nuclear Medicine(NM), unsealed radionuclides are administered to patients for imaging and therapy. Activity administered for therapy is few order higher as compared to diagnostic procedures. Sensitive radiation detectors are installed at major sea-ports, and airports in India. Subsequent to NM procedures, residual radioactivity in patient might trigger these detectors. Further, the belongings of the patient may get contaminated. NM patients being held at Indian airports have been reported in recent time. Security official engaged in screening must distinguish medical use from illicit transport of radioactive materials. Materials and Methods: A holistic review of current regulations for discharging patients following radionuclide procedures was conducted. A survey was conducted with 10 hospitals nationwide that perform such procedures. Further, an in-depth literature review was conducted to gather insights from international best practices. Using these as input, a procedure is developed for security officials.
Results:
Procedure to be followed by Security officials:
7. Once the radiation detector gives an alarm/indication, radiation level@1m from the individual should be checked.
8. If the radiation level at 1m is below 50 µSv/h from an individual or his/her belongings, the radiation might be due to some medical procedures with radionuclides.
9. In case of radiation levels more than 50 µSv/h, DAE-ECR may be consulted for further action.
10. If the radiation is not from the individual it might be from his/her belonging. The belonging may be checked for plausible contamination and segregate the contaminated materials. If no contamination found, the case need to be investigated in detail.
11. If, the individual informs that the radiation is from medical procedure, ask for the travel card issued by the hospital at the time of discharge.
12. If required, the contacts mentioned on the card may be contacted for further clarification w.r.t. to the medical procedure.
A clear delineation of the roles and responsibilities NM Physicians/RSOs, and patients
Role of the NM Physician/ RSO:
5. Prior to administering the activity, counsel the patient about the possible issues during their travel after the therapy.
6. Provide the patient with travel card that have the information such as patient name, date of treatment and discharge, radiation level@1m from the patient at the time of discharge, contact number of concerned Physician/RSO etc.
7. At the time of discharge, the RSO should ensure that belongings of the patient are free from radioactive contamination.
8. Provide inputs to the security official w.r.t. the radionuclide procedure as and when needed.
Role of the patient:
Carry the travel card during traveling subsequent to radionuclide procedures.
Arrange to get all the personal belongings used during the treatment checked for contamination before leaving the hospital.
Conclusion: The procedure aids security officials in distinguishing medical use from illicit radioactive material transport. It encourages cooperation from NM professionals to streamline security checks at places like airports, improving traveler screening and security.
Other 37: Emerging indication of 99MTC-MDP bone scan with SPECT/CT in rheumatology – A case of poems syndrome
Sanisetty Sarath, Dr. S Sanisetty1, Dr. P Rawat1, Dr. B Jatteppanavar2, Dr. Venkatesh S Pai2, Dr. M L Narayan1*
Department of Nuclear Medicine1, General Medicine2, All India Institute of Medical Sciences, Rishikesh, U.K
Introduction: POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Plasma Cell Disorder, Skin Changes) syndrome or Crow-Fukase syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The production of pro-inflammatory cytokines is thought to play an important role in the pathogenesis of POEMS syndrome. Differentiating features of POEMS syndrome from standard multiple myeloma (MM) includes - (1) dominant symptoms of neuropathy & endocrine dysfunction (2) dominant symptoms have little to nothing, to do with bone pain, extremes of bone marrow infiltration by plasma cells (3) high vascular endothelial growth factor (VEGF) levels; (4) sclerotic bone lesions are present in the majority of cases; (5) overall survival is typically superior; and (6) lambda clones predominate in POEMS syndrome. Imaging with 18F-FDG PET/CT & 68Ga-Pentixafor PET/CT are investigation of choice in POEMS syndrome and related disorders. Authors here present a case where an inexpensive, easily available 99mTc-MDP Bone scan (SPECT-CT), helped in providing the correct diagnosis and guided the clinicians for an appropriate treatment and management in this case. Materials and Methods: A 46 years old male patient with pure motor axonal type polyneuropathy affecting bilateral upper limbs, hepatosplenomegaly, lymphadenopathy, moderate aortic stenosis- bicuspid aortic valve, mild aortic regurgitation and mild pulmonary arterial hypertension with clinical suspicion of Multicentric Castleman disease (MCD) vs POEMS syndrome was referred to Nuclear Medicine Department for 99mTc-MDP Bone scan. Three phase 99mTc MDP bone scan was performed using standard protocol with whole body planar and SPECT/CT imaging. Images were analyzed by an experienced Nuclear Medicine Physician. Results: Whole body bone scan showed mild diffusely increased osteoblastic activity involving axial skeleton & periarticular region of long bones. Moderately increased radio-tracer uptake was also noted involving bilateral shoulder, wrist, hip, knee, sacroiliac, knee and ankle joints suggesting active arthritic changes. Mild diffusely increased tracer activity seen in the axial skeleton which could possibly be due to reactive changes, consequent to coexistent marrow infiltrative pathology. Co-registered SPECT/CT (limited section) images reveal multiple tiny sclerotic lesions involving body of L-1, L-2 lumbar vertebrae, left iliac bone, right acetabulum & right proximal femur but there was no significant radiotracer abnormality at these sites. This finding of multiple sclerotic lesions of < 10 mm size fullfilled one of the major diagnostic criteria of POEMS syndrome proposed by Angela Dispenzieri et al. Conclusion: 99mTc-MDP SPECT/CT scan in this index case helped in identifying the sclerotic lesions, that favored and confirmed the diagnosis of POEMS syndrome over Multiple myeloma. Although, 18F-FDG PET/CT, 68Ga-Pentixafor & newer tracers 68Ga-FAPI would be better in localizing the bone marrow, extraosseous involvement and inflammation at molecular level in POEMS syndrome that proceeds structural changes detected by CT or MRI. But here in this case bone scan has helped in localizing osteosclerotic lesions and extent of skeletal involvement, that fulfilled one of the major diagnostic criterion and thereby helped in the diagnosis and management of disease.


Other 38: A rare case of intra-abdominal lymphangioma presented with chylous pleural effusion: Pivotal role of Lymphoscintigraphy
Priyanka Rawat, Dr. Pradeep P.1, Dr. Manishi L Narayan1*, Dr. B. Satya Sree2, Dr. P. Kothari2
AIIMS, Rishikesh
Introduction: Lymphoscintigraphy (LSG) is a valuable diagnostic modality for assessment of lymphedema, chyle reflux and leakage. Bourgeois et al emphasized the usefulness of LSG to demonstrate the chyle leak and reflux, delineating the exact anatomical connections among the lymphatic structures for evaluation of lymphangiomas. Authors, here present a rare case of intra-abdominal lymphangioma in a young adult male, who presented with recurrent chylous pleural effusion and the role of LSG in characterization of lesion, localization of lymphatic leak and establishing the pre-operative diagnosis. Materials and Methods: 16 year old male, presented with complaints of abdominal distension, associated with abdominal pain, fever, cough, chest pain and gradually progressive shortness of breath for over 2 months. Chest X-ray revealed right sided massive pleural effusion, for which intercostal drainage (ICD) was inserted. On pleural and ascitic fluid aspiration, cytology revealed, milky white fluid consistent with chyle leak into pleural and abdominal cavity (Table-1: Complete Lab profile). CE-MRI showed a multiloculated intraabdominal cystic mass lesion with extension into retroperitoneum and thoracic cavity with suggesting possibility of lymphatic malformations. LSG scan was performed following intradermal injection of 1 mCi of 99mTc- Sulfur colloid (filtered) into 1st and 2nd interdigital web spaces of bilateral lower limbs. LSG revealed normal ascent of tracer noted from bilateral lower limb. Followed by an ill-defined focus of abnormal, progressive tracer pooling, noted in left side of abdomen with persistent tracer retention upto 24 hours. Mild tracer localization also noted in right hemi thorax. This abnormal tracer localization was also confirmed by presence of radioactivity (Gamma well counter) in the pleural fluid sample from ICD drain. Faint tracer leak was also noted in the peritoneal cavity at 24 hrs. Chylous pleural effusion could, possibly be due to abnormal peritoneo-pleural communication. This child was managed conservatively with gradual drainage of chylous pleural and ascitic fluid, he was started on parenteral nutrition and injection octreotide. In view of poor response to above management, surgical excision of the lymphangioma was planned. Exploratory laparotomy revealed large lymphangioma (15×12×10cms), occupying whole of lesser sac with multiple enlarged mesenteric lymph nodes and chylous fluid collection in the Morrison's pouch. Additionally, three other sites of lymphangiomas were noted, arising from the anti-mesentric border of transverse colon, splenic flexure and descending colon. Bleomycin injection was given intra-operatively at the lymphangioma bed and pelvic drain was placed. Histopathological examination confirmed the diagnosis as lymphangioma of lesser sac and the large intestine. Patient was discharged on antibiotics, medium chain triglycerides and high protein, fat-free diet with pelvic drain in-situ. Patient remained asymptomatic for a period of 4 months, later he had an episode of chyloperitoneum which was drained. Since then patient is asymptomatic, he is advised dietary modifications and for close follow up. Lymphangiomas usually appear in the head, neck, and axillary regions, most often in children. Abdominal lymphangiomas are extremely rare with a reported incidence of 1 in 20,000 to 250,000. Less than 1% of patients present with cystic lymphangiomas in mesentery, greater omentum and retroperitoneum. LSG can play an important role in confirmation of cystic masses with suspicion of lymphangioma. It can also help in detecting additional sites of involvement as seen in congenital malformations of lymphatic vessels. Through this case authors, emphasize the pivotal role of LSG as an important pre-operative imaging tool for suspected lymphangioma, to localize sites of dilated ectatic lymph channels, extent of local involvement, possible chyle leak and reflux into peritoneal, pleural cavities or abnormal peritoneo-pleural communication. This significantly contributed to confirming the diagnosis and had a positive impact on optimal surgical management.
| Haemoglobin | 12 gm% | Serum total cholesterol/Triglycerides | 81/50 mg/dl | |
|---|---|---|---|---|
| Total leukocyte count | 5700 cells/mm3 | Pleural fluid | Triglycerides | 1186 mg/dl |
| Platelet | 279×103 cells/mm3 | Cholesterol | 90 mg/dl | |
| Total Protein | 7.2 g/dl | Ascitic fluid | Triglycerides | 887 mg/dl |
| Serum Albumin | 4 g/dl | Cholesterol | 71 mg/dl | |
| Urea/Serum Creatinine | 13/0.54 mg/dl | Culture and CBNAAT of pleural fluid and ascitic fluid | Sterile (Negative for Tuberculosis) | |
Other 39: The role of SPECT/CT in the diagnosis of the patient with foot and ankle pain presenting at AIIMS Rishikesh – A diagnostic validation study
K. Vidhya, Shranav Jha, Hardik Veerwal, L. S. Sanjith, Nikhil Kumar Gupta, Vandana K. Dhingra
Department of Nuclear Medicine, AIIMS, Rishikesh, Uttarakhand, India


Introduction: Diagnosing the cause of foot and ankle pain can be challenging due to the complex anatomy. MRI is commonly used for its high resolution and sensitivity, especially for conditions like ligament injuries, impingement, and bone issues. However, it has limitations, including issues with multiple lesions and claustrophobia. To address this, 99mTc labelled phosphates have been used, enhancing localization in lesion identification. SPECT/CT combines functional lesion identification with anatomical localization, offering a comprehensive image. This hybrid approach is particularly valuable when conventional methods yield inconclusive results. Overall, it provides an effective solution for diagnosing foot and ankle disorders. Methods: Patients referred to nuclear medicine department from the foot clinic were interviewed and a through clinical history, examination was performed. SPECT/CT and MRI of foot were performed for all the patients. The MRI and SPECT/CT images were evaluated by an expert radiologist and Nuclear Medicine physician, respectively. Lesions detected were divided into– bone, joint and ligament/tendon lesions, based on imaging findings. Considering the findings in the MRI as gold standard, overall as well as lesion specific sensitivity, specificity, PPV and NPV were calculated for SPECT/CT. Results: In this study with 17 patients (13 males, 4 females; mean age 37.9 years), the time between SPECT/CT and MRI ranged from 3 to 43 days. Pain locations included ankle joint (10 patients), forefoot (3), midfoot (3), and hindfoot (1). Collectively, SPECT/CT, MRI, or both detected 69 lesions. SPECT/CT found 49 lesions(18 bone, 13 ligament/tendon, 18 joint lesions), while MRI found 52 lesions (17 bone, 22 ligament/tendon, 13 joint lesions). SPECT/CT detected more bone and joint lesions compared to MRI. Of all lesions, 15 were found by MRI only, 12 by SPECT only, and 37 were identified by both. Sensitivity, specificity, PPV, and NPV of SPECT/CT as compared to MRI for joint lesions were 92.3%, 40%, 66.7%, and 80% respectively. For bone lesions, they were 76.5%, 28.6%, 72.2%, and 33.3% respectively. Overall, sensitivity, specificity, PPV, and NPV of SPECT/CT as compared to MRI were 71.1%, 45.4%, 75.5%, and 40% respectively. Conclusion: This study concluded that SPECT/CT can be used as an effective tool for the assessment of foot and ankle pain. In a subgroup of patients with foot and ankle pain, the study concluded that -
SPECT/CT has a comparable diagnostic performance to MRI especially in joint and bone lesions
SPECT/CT can be used as an initial modality for the assessment of foot and ankle pain patients to direct the need of MRI for further evaluation
SPECT/CT had a significant impact on the treatment and management of the patients in this study.
| SPECT/CT | MRI | |||
|---|---|---|---|---|
| Type of lesion | No of lesions | (%) | No of lesions | (%) |
| Bone | 18 | 36.7 | 17 | 32.7 |
| Ligament/tendon | 13 | 26.6 | 22 | 42.3 |
| Joint | 18 | 36.7 | 13 | 25 |
| Total | 49 | 100 | 52 | 100 |
| MRI (+) | MRI (-) | Total | |
|---|---|---|---|
| SPECT/CT (+) | 37 | 12 | 49 |
| SPECT/CT (-) | 15 | 10 | 25 |
| Total | 52 | 22 | 74 |
Other 40: Iodine uptake patterns on pre-ablation whole body scans are related to elevated serum thyroglobulin levels in patients with differentiated thyroid carcinoma
Gurudas Singh, Meet Patel, Shubham Dadhich, Himanshu Bansal, Priya Sharma, Chaitanya Kalani
Department of Nuclear Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, India
Introduction: A diagnostic I-131 (Dx) scan is a non-invasive method used to detect a thyroid remnant or metastases before treatment of differentiated thyroid cancer (DTC) with I-131. The visualization of the target allows for precision therapy. This study was conducted to identify prognostic factors in patients with differentiated thyroid cancer (DTC) at the time of first radioactive iodine (RAI) therapy. The authors studied the relationship between the iodine uptake pattern on pre-ablation whole body scan(DxWBS) and thyroglobulin levels in patients with differentiated thyroid carcinoma. Materials and Methods: The study subjects were patients with DTC had undergone total thyroidectomy and were on thyroid hormone withdrawal after thyroidectomy. Serum Tg was checked before RAI therapy (pre-ablation Tg). Patients were classified into two groups according to the presence of tracer uptake on DxWBS - on thyroid bed (group 1) or thyroid bed+ extra thyroid uptake (group 2). Variables were subjected to analysis to identify differences between the two groups. Results: Thirty-five patients were enrolled in this study; 30 in group 1 and 5 in group 2. Based on univariate analysis, pre-ablation Tg (12.23 ± 7.45 vs. 83.58 ± 29.63) were significantly higher in group 2. On the other hand, gender, tumor (T) stage, lymph node (N) stage, size, multiplicity or bilaterality of primary tumor and thyroid-stimulating hormone (TSH) level (before RAI therapy) were not significantly different in the two groups. Conclusion: Serum Tg level before RAI therapy was significantly higher in patients with thyroid + extra thyroid uptake on DxWBS, compared with patients with only thyroidal bed uptake on DxWBS. Further investigations with more number of patients is needed to reveal the correlation between serum Tg elevation and clinical outcome according to the uptake pattern on pre ablative DxWBS.
Other 41: Assessing renal obstruction: A comparative study of ultrasound and diuretic renal scans
Surya Pratap Singh, Surya Pratap, Vijay Singh, Manish Ora, Sanjay Gambhir
Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: Assessing renal function and detecting urinary tract obstruction are crucial for managing renal diseases. Untreated obstructive uropathy can lead to irreversible renal damage and chronic kidney disease. Ultrasound (USG) is a non-invasive, inexpensive, and widely available imaging that provides valuable information about renal anatomy. However, USG alone may not confirm or exclude renal obstruction, especially in partial or intermittent obstruction cases. Therefore, functional tests are needed to evaluate the renal excretory function and drainage to preclude obstruction. Renal Diuretic radionuclide scan is among the most commonly used nuclear medicine techniques. It quantitatively measures renal perfusion, function, drainage, and obstruction. We compared the USG and diuretic renogram parameters of obstructions. Materials and Methods: This study retrospectively encompassed a cohort of 49 patients. Comprehensive baseline demographic information, including age, gender, and pertinent medical history, was meticulously collected. A clinical and biochemical evaluation incorporates a detailed medical history, physical examination, and laboratory tests. The USG kidney included the most commonly used obstructive renal parameter, i.e., the renal pelvis's anterior-posterior diameter (APD). These measurements were obtained adhering to standardized protocols. Renal Diuretic 99mTc EC scans were performed on each patient. The procedures adhered to established clinical guidelines, including the intravenous injection of Tc-99m EC and furosemide as per the patient's weight. Imaging sequences commenced with perfusion images acquired over 1 minute (2 seconds per frame), followed by cortical uptake and drainage phase images captured over 20 minutes. Post-void images were obtained immediately after the drainage phase, followed by delayed images taken 2 hours later. All acquired data were meticulously analyzed on XELERIS workstations. Results: Total patients were 49, and 41 (84%) male. The mean and median APD were 3.0 cm and 3.2 cm, respectively, with a standard deviation of 1.81 cm. Based on APD, we classified the patients into two groups: less than 2.5 cm (16 patients, 33%) and more than 2.5 cm (33 patients, 67%). Renal scans were categorized as obstructive (21 patients, 43%) or non-obstructive (28 patients, 57%). Among the patients with an APD≥ 2.5 cm, 17 (51%) had non-obstructive, and 16 (49%) had obstructive drainage. Among the patients with APD <2.5 cm, 12 (75%) had non-obstructive drainage, and 4 (25%) had obstructive drainage. Pearson correlation coefficient and the Point biserial correlation for the APD with the 20 min to peak ratio and renal diuretic scan findings were calculated. The results showed a weak positive correlation (r = 0.205, p value = 0.158), with no significance between the APD and the 20-minute-to-peak ratio. There was a significant (p valve = .001) but negative medium correlation (r = -0.446) between the APD and obstruction on the renal diuretic scan [Table 1]. Conclusion: Current study findings suggest that USG measurement of APD alone is unsuitable for documenting or refuting renal obstruction. Based on size criteria of >2.5 centimeters, more than half of the patients are falsely diagnosed as obstructive. Severe patients have obstruction despite low APD, possibly due to tight stricture with a poor compliant pelvis. Diuretic renal scan remains an indispensable and complementary study in hydronephrosis management.
| Parameters | Correlation | APD (cm) |
|---|---|---|
| 20 min/peak ratio | Pearson correlation | 0.205 |
| Significant (two-tailed) | 0.158 | |
| Presence/absence of obstruction on final impression | Pearson correlation | −0.446 |
| Significant (two-tailed) | 0.001 |
APD: Anterior-posterior diameter
Other 42: Correlation between thyroid liver ratio and %radioactive iodine uptake: Thyroid liver ratio as a marker of residual or remnant disease
Mehul Dulet, Deepanksha Datta, Rajesh Kumar, Sameer Taywade
Department of Nuclear Medicine, AIIMS, Jodhpur, Rajasthan, India
Introduction: Serial thyroglobulin (TG) measurements is used to monitor residual or metastatic disease in the post surgery status of thyroid cancer as it reflects the overall disease burden load in the body. Evidence of structural disease on low dose whole body iodine scan is a prerequisite for radioiodine ablation, and is also important for assessing the response to therapy. Physiological uptake of radioiodine in liver in the whole body iodine scan is likely due to the hepatic metabolism of thyroglobulin. With this study, we analyse the relationship between the non-invasive parameter of thyroid remnant to liver ratio on low dose whole body iodine scan with the radio-iodine uptake. Materials and Methods: It is retrospective study done in the department of Nuclear Medicine at AIIMS, Jodhpur. Those patients with known thyroid cancer and post total thyroidectomy status who underwent low dose whole body radioiodine scan and radioiodine uptake at 24 hrs were included in the study. Thyroid to liver ratio (TLR) was calculated for each patient by dividing the counts of thyroid remnant with that of liver on radioiodine scan. Correlation between the TLR and radioiodine uptake was done using Spearman coefficient, and p value of less than 0.05 was considered significant. Results: 13 patients met the inclusion criteria, median age of 36 years, male to female ratio of 1:3, median TLR was 4.37 and median radioiodine uptake was 2.6%. Significant positive correlation was found between the TLR and radioiodine uptake with r value of 0.89 & p value <0.05. Conclusion: Thyroid to Liver Ratio (TLR) can serve as an indirect non-invasive marker to assess the burden of the thyroid cancer disease.
Other 43: [11C]Methylated Analogue of Epileptic drug Levetracetam: An Automated Synthesis and Quality Assurance studies
Mohd. Faheem, Omkar Chauhan, Sanjay Gambhir Manish Dixit
Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: Epilepsy, a widespread neurological disorder affecting roughly 50 million people worldwide, characterized by epileptic seizures caused by abnormal brain electrical activity. Its diagnosis involves a comprehensive evaluation, including medical history, physical exams, and diagnostic tests like imaging. Researchers have explored radiopharmaceuticals like 11C-flumazenil, 18F-MPPF, 11C-Cerfentanil, and 11C-MeNTI to target specific receptors and neurotransmitters for localizing epileptogenic foci through PET/CT or PET/MRI imaging. Levetiracetam (LEV) is an epileptic drug that binds with SV2A-based receptors. Its mechanism is still under on-going research and may effect on calcium homeostasis, GABAergic system and AMPA receptors. This study focused on synthesis and quality assurance of radiolabeled analogue of Levetiracetam with [11C]Carbon radionuclide, for PET-based brain studies, aiding in locating epileptogenic foci. Prior to synthesis, computational studies were conducted to refine the methylated LEV's design, in order to assess the targets synaptic vesicle protein SV2A binding, modulating neurotransmitter release and reducing seizures. Materials and Methods: All the chemicals were purchased from commercial sources and are used as such. No carrier-added [11C]CO2 was produced through 14N(p,n)11C nuclear reaction using an 18MeV proton (HM-18 SHI, Japan) and transferred to an automated synthesis module MPS100 (SHI, Japan) with the stream of nitrogen and used for synthesis of [11C]Methylated LEV synthesis. For the automated [11C]methylation of Levetiracetam in CFN-MPS100 synthesizer two methods were adopted and compared. The methlating agent [11C]CH3I and [11C]CH3OTf were produced as per literature reported method with slight modifications.(Jewett et al.'s 1992). The Radiolabeling was characterized by analytical tools.

Results: In this study, the radiolabeling of [11C]CH3 on NH2 functional group of Levetiracetam's analogue was explored via. two routes using [11C]CH3I & [11C]CH3OTf as methylating agent. The methylation via [11C]CH3I or [11C]CH3OTf gives 70.0 mCi or 90.0 mCi respectively in 15.0 min at EOB and radiochemical purity of ≥95%. The [11C]methylated LEV were analyzed by HPLC equipped with radiation detector, at 0.7 ml/min flow rate using 75:25 acetonitrile/water as mobile phase. The cold methylated LEV with co-elution radiolabeled analogue was also analyzed with retention time of 6.16 min. All other quality control tests were performed such as half-life, pH, radionuclide purity and sterility to qualify for clinical application. Conclusion: We successfully automated the processes by two methods using [11C]CH3I or [11C]CH3OTf for methylation of Levetiracetam. The isolated product has good yield and purity. The radiolabeled Levetiracetam may be further explored for imaging patients.
Acknowledgement: This facility has been funded in whole by Government of Uttar Pradesh and SGPGIMS. I sincerely thanks Mrs Sarita Kumari, and Mr Umesh Singh for the production of radioisotopes.
Other 44: Advanced understanding of POEMS syndrome: A comprehensive case study and imaging evaluation using F-18 FDG PET/CT
Harrish, Vijay Singh, Manish Ora, Sanjay Gambhir
Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: POEMS syndrome is a rare paraneoplastic syndrome caused by an underlying plasma cell disorder. It is characterized by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin abnormalities. Common symptoms include progressive weakness of the nerves in the arms and legs (sensorimotor polyneuropathy), hepatosplenomegaly, enlarged lymph nodes (lymphadenitis), hyperpigmentation, thickening of the skin, and hypertrichosis. Polyneuropathy and Monoclonal gammopathy (Lambda) is mandatory criteria, Sclerotic bone lesion, Castleman disease elevated anti-VEGF are major criteria, and organomegaly, endocrinopathy, skin changes, optic disc swelling, and polycythemia are minor criteria for the diagnosis. FDG PET/CT is a valuable modality in these patients’ diagnosis, evaluation, and follow-up. It provides systematic findings of bone lesions, lymphadenopathy, liver or spleen involvement, serous cavity effusion, and the metabolic status of the lesions. Biopsy and final diagnosis could be made by guided approach. Materials and Methods: This study presents three cases of POEMS syndrome, all presenting with demyelinating neuropathy. Comprehensive evaluations were analyzed, including the patient's history and biochemical and hematological parameters. F-18 FDG PET/CT was performed, and imaging findings were assessed to aid in an inconclusive diagnosis. Follow-up FDG PET/CT was conducted to evaluate treatment responses. Results: Case 1: A 48-year-old male patientpresented with demyelinating neuropathy. Hepatosplenomegaly was noted. Lymph node cytopathology and bone marrow aspirate were inconclusive. FDG PET/CT revealed hepatosplenomegaly with metabolically activemultifocallytic skeletal lesion. PET/CT-guided biopsy suggested plasma cell infiltration. Lymph node biopsy suggested the Castleman variant of POEMS. Post-diagnosis7 cycles of RVD regimen chemotherapy were given. The patient was asymptomatic. Follow-up PET/CT was done, which revealed a complete metabolic response. Case 2: A 24-year-old male presented a burning and tingling sensation with bilateral lower limb weakness. A diagnosis of demyelinating disorder was made. He had lymphadenopathy. FDG PET/CT revealed multiple axillaryand mediastinal lymph nodes with hepatosplenomegaly and metabolically active (SUV-11.5) multiple skeletal lesions (Right scapula, left acetabulum, left ischium). A biopsy was done on the skeletal lesion, which revealed plasmacytoma. The patientstarted on a VCD regimen, and on completion of chemotherapy, repeated PET/CT suggested residual disease. The patient is receiving a KPD regimen of chemotherapy. Case 3: A 43-year-old male patient presented gradual onset progressive difficulty getting up from a squatting position and imbalance during walking. MRI suggestive of demyelinating neuropathy. Serum electrophoresis was inconclusive. Suspicion of POEMS syndrome was raised. FDG PET/CT revealeda metabolically active rib lesion with multiple cervical lymph nodes with hepatomegaly. Biopsy from rib lesion suggestive of plasmacytoma, and patient started on VRD regimen. Conclusion: In a young patient presenting with neuropathy and organomegaly, endocrinopathies and monoclonal gammopathy should be evaluated. FDG PET/CT could be helpful to guide a site for biopsy, especially in nonsecretory plasmacytoma or multiple myeloma. These cases demonstrate that PET/CT can aid in diagnosing POEMS syndrome by detecting metabolically active lesions, guiding biopsy for supporting major criteria of POEMS syndrome. It helps in evaluating treatment response and further management.
Other 45: Impact of renal reserve on glomerular filtration rate in Voluntary kidney donors
Madhur Rai, Vijay Singh, Manish Ora, Sukanta Barai, Sanjay Gambhir
Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: Kidney transplantation, a life-saving procedure for recipients, raises questions about the long term consequences for donors, especially in terms of their renal function. Previous research has predominantly concentrated on short-term outcomes, leaving a gap in understanding the relationship between renal reserve volume and glomerular filtration rate (GFR) after transplantation. This study seeks to address this gap by investigating how pre-transplant renal reserve influences post-transplant GFR over an extended period. Materials and Methods: In this retrospective cohort study, 64 voluntary kidney donors were examined before and after transplantation (6 months post-surgery) to assess the impact of kidney donation. Pre-transplant glomerular filtration rates (GFR) were measured, and renal reserve was calculated. Baseline GFR and ‘stimulated GFR’ following amino acid infusion, were measured in voluntary kidney donors by measuring plasma clearance of Tc99m- diethyl-triamine-penta-acetic acid. Any obtained difference was considered as RR and expressed as a percentage. Participants were categorized into two groups A and B: those with less than 10% renal reserve volume (A) and those with more than 10% (B). Post-transplant GFR values were obtained and compared to pre-transplant values. The percentage increase in GFR was calculated for each participant. Correlation analysis was performed using SPSS software. Results: Out of 64 patients, 46 (72%) were female and 18 (28%) were male. The mean donor baseline GFR was 75 ml (SD ± 13.6). The mean post-transplant GFR was 52 ml (SD ± 10.5). The mean% change of GFR in the remaining kidney was 42% (SD ± 26). The mean renal reserve was 11.3 ml (SD ± 20.3). In 33 patients (58%) renal reserve was found to be less than 10% of baseline GFR and more than 10% in 31 patients (42%). The mean donor baseline GFR of the remaining kidney in group A was 39 ml (SD ± 7.7) and in group B was 34 ml (SD ± 5). The mean post-transplant GFR in group A was 53 ml (30-74, SD ± 8.7), and in group B was 51 ml (30-75 ml, SD ± 12.2). There was 37% mean increase in GFR in remaining kidney noted in group A and 47% increase in group B although the results of correlation were not quite significant in both groups. The correlation value was 0.089 in group A and 0.005 in group B [Table 1]. Conclusion: The study confirms that kidney donors experience a significant increase in glomerular filtration rates (GFR) in the remaining kidney after transplant, indicating the remarkable adaptability of the remaining kidney. In this study donors with a higher renal reserve volume, particularly those exceeding 10%, exhibit a more substantial increase in post-transplant GFR but the correlation between the increase in GFR and RR was not quite significant. This highlights that the role of renal reserve in predicting and understanding the enhancement of renal function post-transplant is not as important as it may seem to be although more studies are required for further confirmation. It is possible that factors other than renal reserve plays a significant role in recovery of renal function following kidney transplant in donors.
| Correlation | Parameters | Value |
|---|---|---|
| Group A (Renal reserve <10%) | Person correlation | 0.089 |
| Significance | 0.621 | |
| GROUP B Renal reserve <10%) | Person correlation | 0.005 |
| Significance | 0.978 |
Category: Therapy
Therapy 1: Preparation and evaluation of 90Y superficial patch for treating skin tumors and keloids using low specific activity 90Y produced by direct activation route
K. V. Vimalnath, A. Rajeswari, S. P. Lohar, Sudipta Chakraborty
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
Introduction: Superficial skin tumors, a majority of which are basal cell carcinomas, and keloids are of serious concern. Radiotherapy by the external use of radioactive skin bandage or patch on the disease site is one of the most promising curative modalities. Previous works in this direction have reported preparation and use radioactive patches based on radioisotopes such as no-carrier-added 32P. Herein, we report the preparation, quality control and use of radioactive skin patches utilizing low specific activity 90Y produced by direct activation route as a cost-effective alternative for commercial deployment. Materials and Methods: Y-90 was produced by irradiating 10 mg Y2O3 at 1.2×1014 n/cm2/s flux in Dhruva research reactor for 7 d. Radiochemical processing is carried out inside a 100 mm lead shielded glove box facility with remote handling provisions to convert irradiated Y2O3 to [90Y]YCl3 solution. Typically, 5 µL [90Y]YCl3 containing ~ 111 MBq (3 mCi 90Y) was immobilised on a circular cellulose substrate (Whatman-541) having 25 mm diameter. The preparation was air dried and sealed completely from both sides using an adhesive regenerated transparent cellulose strip. Activity content of [90Y]YCl3 and 90Y-patch prepared is ascertained by measurements in a dose calibrator. Determination of surface contamination, autoradiography studies of the 90Y patch prepared were carried out to ascertain the suitability of the preparation for clinical use. Further, leaching of 90Y and radiation stability of the patches were studied upto 5 half-lives of 90Y to evaluate the integrity of the product. Results: Y-90 was produced direct activation route with 22 ± 3 mCi /mg specific activity in 7 d irradiation protocol at highest available thermal neutron flux of Dhruva research reactor. Radiochemical processing yielded [90Y]YCl3 solution with radioactivity concentration 400mCi 90Y/mL suitable for preparation of patches of ~ 111 MBq source strength 24 h after irradiation of target. The radioactive 90Y-patches were tested surface contamination by swiping the sources using cotton wool immersed in alcohol and measuring the radioactivity associated with swipes in a pre-calibrated radioactivity counter and no surface contamination was detected. Autoradiography of 90Y in radioactive patches checked by using industrial X-ray films revealed that optical density was consistent at various points of exposed film which confirmed that 90Y activity is almost uniformly distributed throughout the source, a prerequisite for its clinical use. Leach studies of 90Y activity monitored for 14 d (~5 half-lives) showed that only 9×10-5 % of total activity is leached out into phosphate buffered saline (PBS) in the said period, which is very insignificant. The patches were stable during the period of studies and had not showed and physical deterioration in flexibility or integrity of sealing. The patches were evaluated for its therapeutic effectiveness by using in human patients with superficial keloid lesion. The patches were placed over the affected area in close proximity for optimised durations of exposure. The preliminary outcome of the study is promising in terms of improvement of disease condition. Conclusion: Our results show that the 90Y-patch designed by utilising low specific activity 90Y as a contact brachytherapy source is easy to prepare and effective in the treatment of skin diseases. Direct activation route of production ensures a high purity [90Y]YCl3 radiochemical suitable for preparation of patch without the intricacies of handling long-lived 90Sr. Clinical outcome shows that it could be commercially deployed as a superficial patch source at affordable cost in large numbers for treatment of patients.
Therapy 2: Formulation, deployment and clinical use of [90Y]Yttria Alumino Silicate Glass microsphere aka “Bhabhasphere” in the management of liver cancer in India
Sudipta Chakraborty, K. V. Vimalnath, A. Rajeswari, Anupam Dixit, S. P. Lohar, Rubel Chakravarty, Madhumita Goswami
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
Introduction: Selective internal radiation therapy (SIRT) using a suitable b- emitting radionuclide is a promising treatment modality for unresectable liver carcinoma. Intrinsically radiolabeled [90Y]Yttrium glass microsphere formulation (TheraSphere®) is approved by US FDA for the treatment of primary liver cancer is available commercially. However, high cost of this product severely restricts its utility in countries such as India. Working toward indigenous development of [90Y]Yttrium glass microsphere formulation which can be made available at an affordable cost for liver cancer patients in India, we have developed biosimilar product [90Y]Yttria Alumino Silicate (YAS) glass microsphere (‘Bhabhasphere’) and translated to clinics. Materials and Methods: YAS glass microspheres of composition 40Y2O3-20Al2O3-40SiO2 (w/w) and diameter ranging between 20-36 µm were synthesized by flame spheroidization process with almost 100% conversion efficiency and >99% sphericity. Intrinsically labeled [90Y]YAS were produced by irradiating typically 50 mg cold YAS glass microspheres at neutron flux of 1.4×1014 n.cm-2.s-1 for 7 d in Dhruva research reactor, Trombay. After 24 h of cooling, [90Y]YAS microparticles were retrieved from quartz ampoule and suspended in sterile physiological saline. The contents were vortexed, centrifuged, supernatant carefully withdrawn and discarded. [90Y]YAS microspheres were reconstituted in 0.6 mL sterile physiological saline and measured in a pre-calibrated dose calibrator to ascertain the 90Y radioactivity. Measured aliquots of [90Y]YAS was fractionated into custom designed sterile glass vials, sealed and autoclaved (20 min at approximately 121°C and 15 psi pressure). About 15 Customized doses of [90Y]YAS with 90Y activity ranging from 2.6-7.4 GBq were prepared and clinically utilised. [90Y]YAS glass microsphere formulation was prepared and administered through hepatic artery with super selective approach. Results: High degree of sphericity and uniformity of the microspheres were confirmed by SEM images. XRD pattern of synthesized YAS glass microspheres confirmed typical glassy nature of the material. Laser diffraction particle size analysis showed more than 90% of particles were within the range of 20-36 mm. Intrinsically [90Y]Y-labeled YAS glass microspheres were produced with specific activity 140 ± 8 MBq/mg YAS glass (~6800 Bq/microsphere). Radionuclidic purity of formulation was 99.93 ± 0.02 % desirable for human clinical applications. So far, 11 patients were treated using customized dose of the formulation. Yttrium-90 PET scans recorded at different time points post-administration of formulation showed near-quantitative retention in the injected lobe. Administered therapeutic doses of the developed [90Y]YAS glass microsphere formulation injected was well tolerated by the patient, as no adverse side effect of the therapeutic procedure was reported. [90Y]YAS glass microsphere (Bhabhasphere) is now DAE-RPC approved product and commercially deployed through Board of Radiation and Isotope Technology (BRIT) to nuclear medicine hospitals across India. Conclusion: Commercial deployment of ready to use therapeutic doses of [90Y]YAS glass microsphere ‘Bhabhasphere’ suitable for human clinical use in the treatment of unresectable liver cancer is achieved. YAS glass microspheres of composition 40Y2O3-20Al2O3-40SiO2 (w/w) and diameter ranging between 20-36 µm were prepared by flame spheroidization process. [90Y]YAS glass microspheres with adequate radionuclidic and radiochemical purity for human clinical use is produced by thermal neutron irradiation of YAS glass microspheres. Human clinical evaluation in patients with right lobe hepatocellular carcinoma also showed near-quantitative retention of the formulation in the injected lobe by post-therapy 90Y-PET scans without any adverse side effects.
Therapy 3: Biodistribution and dosimetry of indigenously prepared 177Lu-DOTA-rituximab in lymphoma and other hematological malignancies treated with rituximab
Yeshwanth Edamadaka, Rahul Parghane, Vrinda Kulkarni, Chandrakala Shanmukhaiah, Sudeep Sahu, Kamaldeep, Sandip Basu
Radiation Medicine Centre, BARC, HBNI, Mumbai, Maharashtra, India
Introduction: Radioimmunotherapy (RIT) combines immunotherapy and radiation therapy by using specific antibodies binding to target tumor antigens. Bexxar and Zevalin are the most extensively studied and FDA-approved RIT agents for treatment of lymphoma patients.177Lu-DOTA-rituximab offer number of advantages over approved RIT agents. We studied biodistribution and dosimetry of indigenously prepared 177Lu-DOTA-rituximab in NHL and other hematological malignancies treated with rituximab. Materials and Methods: Patients with CD20-positive B-cell NHL and other hematologic malignancies treated with rituximab underwent dosimetry study using low-dose diagnostic scans for indigenous 177Lu-DOTA-rituximab. Patients first received cold rituximab 375 mg/m2, followed by a diagnostic dose of 185-370 MBq of 177Lu-DOTA-rituximab via intravenous infusion in 0.9% normal saline over 15-20 minutes. Planar imaging was acquired at multiple-time points at pre-void and post-void post-infusion (P.I.); 24 h (P.I); 72/96h (P.I). Normal organs and tumor dosimetry was performed by using organ and tumor-specific regions of interest (ROI) and whole-body(WB) counts corrected for background, scatter and attenuation. The software OLINDA/EXM v2.1.1 and ORIGIN 6 were used to obtain dosimetry results. Results: A total 22 patients (M: 14, F: 8, mean age: 49.6 ± 10.5 yrs) were included and analyzed in this study. The mean diagnostic dose administered was 288.6 MBq. Prolonged blood clearances with long residence time in the blood pool and organs (e.g. liver, spleen, kidneys and bone marrow) were noticed. The effective half-life was 104.5 ± 22 h. The mean WB radiation absorbed dose of 0.208 ± 0.03 mGy/MBq and the mean WB effective dose of 0.196 ± 0.05 mGy/MBq of 177Lu-DOTA-rituximab. Liver, spleen, kidneys and bone marrow mean radiation absorbed doses were 0.613 ± 0.21 mGy/MBq, 1.68 ± 2 mGy/MBq, 1.01 ± 0.42 mGy/MBq and 0.136 ± 0.02 respectively. Tumor lesion uptake was visually noticed in two patients, with a radiation absorbed dose of 0.842mGy/MBq and 9.9 mGy/MBq. Therapeutic doses of 177Lu-DOTA-rituximab ranged from 2.35 - 5.25 GBq with a mean dose of 4.07 GBq based upon a whole-body radiation absorbed dose of 75cGy (by using the MIRD schema). Strong correlation (p value<0.001, Pearson's rho = 0.95) between cumulative activities calculated from ORIGIN software and OLINDA software methods was observed. Conclusion: Indigenously produced 177Lu-DOTA-rituximab showed similar biodistribution as compared to the other approved RIT radiopharmaceuticals with hepato-biliary being primary route of clearance and kidneys being the alternate route of excretion. The results of our study on 177Lu-DOTA-rituximab showed favorable biodistribution and dosimetry which includes WB, normal organs and tumor dosimetry by using OLINDA software with validation by ORIGIN software. Hence these results can be utilized for future 177Lu-DOTA-rituximab based therapeutic RIT trials in lymphoma patients.
Therapy 4: [90Y]Y-CHX-A”-DTPA-atezolizumab: A promising therapeutic radiopharmaceutical for PDL-1 overexpressed metastatic large and bulky lesions
S Lad, S. Sahu, S. Lad, M. Tawate, A. Chakrabotry, A. Mitra, S. Rakshit, T. U. Bannore M. K. Ray, S. Basu
Radiation Medicine Centre, BARC, Mumbai, Maharashtra, India
Introduction: Programmed cell death ligand-1 (PDL-1) proteins are overexpressed in a variety of malignancies including cervical carcinoma, small-cell lung carcinoma, breast carcinoma etc. These solid tumors of cervical & small-cell lung origin effectively grow >5 cm, hence such large and bulky lesions could not be treated with any established lines of treatment. In such patients, with advanced-stage solid tumors, [90Y]Y-CHX-A”-DTPA-Atezolizumab is a feasible RIT option. Towards this, clinical dose formulation of [90Y]Y-CHX-A”-DTPA-Atezolizumab was optimized using clinical grade indigenous [90Y]Y-Acetate obtained from nuclear reprocessing waste. The physico-chemical and biological quality control parameters have been optimized. In-vitro pharmacokinetic behavior of this therapeutic agent in cervical carcinoma cell lines (HeLa) and in-vivo pharmacological behavior in severe combined immunodeficiency (SCID) mice with HeLa xenografts with overexpressed PDL-1 were studied to establish the effectiveness of the formulated [90Y]Y-CHX-A”-DTPA-Atezolizumab. The preclinical studies of [90Y]Y-CHX-A”-DTPA-Atezolizumab, reported herein, provides confirmatory indications toward its potential for clinical translation and use in the RIT of PDL-1 overexpressed metastatic carcinomas. Materials and Methods: Clinical grade [90Y]Y-Acetate was extracted from HLLW using two-stage 90Sr/90Y generator system based on supported liquid membrane (SLM) technology. Atezolizumab (100 µL, concentration: 60 mg/mL) were diluted with 400 µL of ultra pure water (UPW) to obtain concentration of 6 mg/0.5 mL. Further pre-concentrated to 90 µL using ultra-centrifugal filters (30 kDa) at 3000g (17 min). Coupling of atezolizumab (6mg in 90 µL, 41.49 nmoles) with p-SCN-Bn-CHX-A”-DTPA (292.08 µg in 29.21 µL, 414.9 nmoles) was carried out at 1:10 molar ratio at pH~8 using 0.2M Na2CO3-NaHCO3 buffer (200 µL), further incubated at 24oC (2h) followed by 4oC (18h). Post conjugation, the crude CHX-A”-DTPA-Atezolizumab was purified and eluted from PD-10 using 0.2M CH3COONa buffer (pH~5.5). pH of [90Y]Y-Acetate (~3.4 GBq) was adjusted to ~6.0 using CH3COONa salt (50 mg / mL of [90Y]Y-Acetate). [90Y]Y-Acetate incubated with purified CHX-A”-DTPA-Atezolizumab at 37oC (90 min). The crude [90Y]Y-CHX-A”-DTPA-Atezolizumab was purified and eluted from PD-10 using 0.2M CH3COONa solution and diluted with saline to maintain RAC of ~0.37 GBq/mL. RCP was evaluated by radio-TLC and radio-HPLC. In-vitro stability was ascertained by adding ascorbic-acid (~240 µg/ 37MBq). Endotoxin limit was quantified by gel-clot BET assay and sterility test was performed by direct inoculation method. In-vitro saline stability was ascertained by evaluating RCP at 24h and 48h post-radiolabeling on storage at -20oC. Human cervical adenocarcinoma cell-line HeLa, expressing PDL-1 was used for in-vitro evaluation. In-vivo biodistribution was carried out in SCID mice bearing tumor xenograft induced by HeLa cell-line. Results: Using ~3.4 GBq of [90Y]Y-Acetate, clinical doses of ~2.9 GBq of [90Y]Y-CHX-A”-DTPA-Atezolizumab (n = 3) were formulated with ~85% radiochemical yield (RCY). 90Y]Y-CHX-A”-DTPA-Atezolizumab was clear and colorless with pH ~4.5-6.0. RCP (radio-TLC, Rf: 0.00-0.10) and (radio-HPLC, Rt: 12–14 min) were >98%. Product was sterile and endotoxin free (EL: < 25 EU/mL). Product was found to be stable upto 48h on storage at -20oC with RCP >98%. [90Y]Y-CHX-A”-DTPA-Atezolizumab showed rapid binding with HeLa cells (~18 ± 3.5%), reaching a plateau after 30 minutes. In-vivo bio-distribution studies exhibited high and long-term retention of [90Y]Y-CHX-A”-DTPA-Atezolizumab in the tumor (5.2 ± 2.5 % ID/gm). Radioactivity from most of the organs decreased within 3 days post-injection. Conclusion: Patient doses formulation of [90Y]Y-CHX-A”-DTPA-Atezolizumab was successfully developed and established. Promising pre-clinical results demonstrates potential for clinical therapeutic application of [90Y]Y-CHX-A”-DTPA-Atezolizumab for RIT of PDL-1 overexpressed metastatic advanced-stage solid tumors in patients.
Therapy 5: Synthesis of [90Y]Y-CHX-A”-DTPA-Bevacizumab & [177Lu]Lu-DOTA-Bevacizumab from Experimental Radiopharmacy: Translation to Clinics for Sequential duo-PRIT of VEGF-A Secreted Solid Tumors
S Lad, S. Sahu, S. Lad, M. Tawate, A. Chakrabotry, A. Mitra, S. Rakshit, T. U. Bannore M. K. Ray, S. Basu
Radiation Medicine Centre, BARC, Mumbai, Maharashtra, India
Introduction: Angiogenesis allows rapid growth of malignant cells in association of new blood vessel formation. Vascular endothelial growth factor A (VEGF-A) is a key factor for inducing tumor angiogenesis. Solid tumor growth is are benefited by new blood vessel formation. Non-homogenous distribution of lesions (size ranging from mm to cm) in metastatic colorectal cancer, renal cell carcinoma and non-small-cell lung cancer could be effectively treated with sequential duo pre-targeted radioimmunotherapy (PRIT) using [90Y]Y-CHX-A”-DTPA-Bevacizumab & [177Lu]Lu-DOTA-Bevacizumab. Herein we report ready-to-use clinical dose formulation of [90Y]Y-CHX-A”-DTPA-Bevacizumab and [177Lu]Lu-DOTA-Bevacizumab. Quality control parameters and in-vitro stability studies were validated. Pre-clinical evaluation involving immunoreactivity, cell binding, internalization and cell surface adsorption was carried out in B16F10 cell lines. Whereas in-vivo biodistribution studies were carried out in tumor bearing SCID mice expressing VGEF receptors (VGEFR). Materials and Methods: [90Y]Y-CHX-A”-DTPA-Bevacizumab: Clinical grade [90Y]Y-Acetate was extracted from HLLW using two-stage 90Sr/90Y generator system based on supported liquid membrane (SLM) technology. Bevacizumab (200 µL, concentration: 25 mg/mL) were diluted with 300 µL of ultra pure water (UPW) to obtain concentration of 5 mg/0.5 mL. Further pre-concentrated to 100 µL using ultra-centrifugal filters (30 kDa) at 3000g (17 min). Coupling of bevacizumab (5mg in 100µL, 33.53 nmoles) with p-SCN-Bn-CHX-A”-DTPA (236.05 µg in 23.60 µL, 335.3 nmoles) was carried out at 1:10 molar ratio at pH~8 using 0.2M Na2CO3-NaHCO3 buffer (200 µL), further incubated at 24oC (2h) followed by 4oC (18h). Post conjugation, the crude CHX-A”-DTPA-Bevacizumab was purified and eluted from PD-10 using 0.2M CH3COONa buffer (pH~5.5). pH of [90Y]Y-Acetate (~4.1 GBq) was adjusted to ~6.0 using CH3COONa salt (50 mg / mL of [90Y]Y-Acetate). [90Y]Y-Acetate incubated with purified CHX-A”-DTPA-Bevacizumab at 37oC (90 min). The crude [90Y]Y-CHX-A”-DTPA-Bevacizumab was purified and eluted from PD-10 using 0.2M CH3COONa solution. [177Lu]Lu-DOTA-Bevacizumab: Clinical grade, carrier added, low specific activity (~0.66 GB/µg) [177Lu]LuCl3 was obtained via 176Lu(n,γ)177Lu nuclear reaction. Dilution, pre-concentration of bevacizumab was carried out as described earlier. Coupling of bevacizumab (5mg in 100µL, 33.53 nmoles) with p-SCN-Bn-DOTA (230.54 µg in 23.05 µL, 335.3 nmoles) was carried out at 1:10 molar ratio at pH~8 using 0.2M Na2CO3-NaHCO3 buffer (210 µL), while incubation and purification of conjugates was carried out similarly as mentioned earlier. pH of [177Lu]LuCl3 (~11 GBq in 0.3 mL) was adjusted to ~6.0 using 0.2 CH3COONa solution (750 µL) and incubated with purified DOTA-benzyl-Bevacizumab at 37oC (90 min). The crude [177Lu]Lu-DOTA-Bevacizumab was purified and eluted from PD-10 using 0.2M CH3COONa solution. RCP was evaluated by radio-TLC and radio-HPLC. In-vitro stability was ascertained by adding ascorbic-acid (~240 µg/ 37MBq). B16F10 cell lines, expressing VGEFR, used for in-vitro evaluation. In-vivo biodistribution carried out in C57BL6 mice bearing melanoma syngeneic tumor induced by B16F10 cell lines. Results: The produced RCY of [90Y]Y-CHX-A”-DTPA-Bevacizumab and [177Lu]Lu-DOTA-Bevacizumab were ~81.42% (n = 3) and 86.9% (n = 4) respectively. The RCP of both the formulations was >98%. In-vitro saline stability for [90Y]Y-CHX-A”-DTPA-Bevacizumab and [177Lu]Lu-DOTA-Bevacizumab was upto 24h and 96h post-radiolabeling at -20oC respectively. Approximately 32 ± 3% rapid binding was observed in B16F10 cells for [90Y]Y-CHX-A”-DTPA-Bevacizumab and [177Lu]Lu-DOTA-Bevacizumab respectively and reaching plateau after 30 minutes. While 8.2 ± 2.7% ID/g accumulation of [90Y]Y-CHX-A”-DTPA-Bevacizumab and [177Lu]Lu-DOTA-Bevacizumab was found in C57BL6 mice bearing melanoma tumor respectively. Radioactivity in most of the organs decreased within 24h and 72h post-injection of [90Y]Y-CHX-A”-DTPA-Bevacizumab and [177Lu]Lu-DOTA-Bevacizumab respectively. Conclusion: The patient dose formulation of [90Y]Y-CHX-A”-DTPA-Bevacizumab and [177Lu]Lu-DOTA- Bevacizumab was successfully developed. Its promise lies in the potential therapeutic application in sequential duo PRIT of non-homogenous VGEFR expressed solid tumors.
Therapy 6: Estimation of serum thyroid stimulating hormone in patients undergoing high dose I-131 therapy after two weeks of thyroidectomy
Joel K Saji, K. K. Kamaleshwaran, E. Ram Kumar, E. R. Radhakrishnan, F. R. Kingsley, Arun Pandian, Suvalakshmi, R. Ruth, M. Sowmiya, R. V. Rithika
Department of Nuclear Medicine, The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India
Introduction: Serum thyroid stimulating hormone (TSH) produced by pituitary gland can be helpful in analyzing thyroid functions and malfunctions. Patients with thyroid cancer (papillary or follicular) can be surgically treated by removing thyroid gland and leaving recurrent tissues to protect the laryngeal nerve, followed by I-131 radio ablation therapy on the basis of I-131 pre therapy scan. Materials and Methods: It's a retrospective study, 25 patients who have undergone thyroidectomy have been analyzed and their serum thyroid stimulating hormone (TSH) was taken after two weeks instead of waiting for three to four weeks to prevent hypothyroid symptoms.
Results:
| Age | Maximum TSH (mIU/L) | Minimum TSH (mIU/L) |
|---|---|---|
| 30–40 | >100 | 37.1 |
| 40–50 | >100 | 38 |
| 60–70 | 40.13 | 30.5 |
TSH: Thyroid stimulating hormone
The above mentioned are the maximum and minimum serum TSH levels for different age groups. Hence from the results it is evident that the ATA guidelines of TSH > 30 can be achieved within two weeks. Conclusion: Within two weeks after thyroidectomy, the serum thyroid stimulating hormone (TSH) levels of patients was above 30 mIU/L. So here we can conclude that we can administer I-131 to patients after two weeks of post thyroidectomy and so there is no need of waiting for three to four weeks.
Therapy 7: Ready-to-use [177Lu]Lu-FAPI-46: Multiple patient dose formulation and its pre-clinical evaluation
A. Mitra, L. Ram, N. Sakhare, A. Chakrabotry1, B. Sanjeevkumar, Seema, S. Mirapurkar, A. Mathur, U. Pandey
Department of Nuclear Medicine, Radiopharmaceuticals Laboratory, BRIT, Navi Mumbai, 1Radiation Medicine Centre, BARC, Mumbai, Maharashtra, India
Introduction: Fibroblast activation protein (FAP) targeted radioligand therapy (TRT), especially with [177Lu]Lu-FAPI-46 or [90Y]Y-FAPI-46 has gained prominence in recent years. These therapeutic radiopharmaceuticals have established a feasible TRT option for advanced–stage solid tumors in cancer patients especially in lesions of pancreatic, colorectal and gastric origin. Towards this, a clinical dose formulation of [177Lu]Lu-FAPI-46 (7-8 patient doses) utilizing 177Lu of medium specific activity was developed and optimized for its clinical end use. In-vitro affinity of this therapeutic formulation towards FAP was evaluated in HT-29 cell lines and in-vivo potential was established in SCID mice bearing HT-29 xenografts. The preclinical studies of [177Lu]Lu-FAPI-46, reported herein, provides positive indications towards its potential for clinical translation and use in the TRT of FAP overexpressed metastatic carcinomas. Materials and Methods: Radiosynthesis of [177Lu]Lu-FAPI-46was carried out on direct addition of[177Lu]LuCl3(~63.5 GBq in 1 mL dil. HCl, 0.63 GBq/µg) to a mixture of FAPI-46 (1.59 µmol, 3.0 equiv. to Lu, 690 µL) and gentisic acid buffered with CH3COONH4 (0.2M, 5.0 mL). The reaction mixture at a pH~4.5 was heated at 100°C for 60 min to yield the desired complex. Radiochemical purity (RCP) of the complex formation was ascertained by PC (CH3CN/H2O: 1/1; Rf: 0.9-1.0), TLC (0.1N sodium-citrate buffer, pH 5; Rf: 0.0-0.1) and reversed phase radio-HPLC (gradient mode, H2O and CH3CN with 0.1% TFA, 1 mL/min; Rt: 14–15 min).[177Lu]Lu-FAPI-46 reaction mixture was suitably diluted with 0.2MCH3COONH4 containing gentisic acid (~20µg/GBq) to yield the final formulation with a radioactive concentration ~0.74 GBq/mL and sterilized using 0.22 µm syringe filter. Endotoxin limit was determined by gel-clot BET assay and sterility test was performed by direct inoculation method. The stability of the [177Lu]Lu-FAPI-46 formulation on storage at -20oCwas ascertained up to a period of one week. The pre-clinical evaluation of the formulation was carried out both in-vitro and in-vivo in FAPexpressingHT-29 cells and HT-29 tumor xenografts respectively. Results: A multiple patient dose formulation of [177Lu]Lu-FAPI-46 (n = 8) could be successfully prepared in high radiochemical yield (RCY~98.11%) using medium specific activity 177Lu. The in-vitro cell uptake studies showed rapid binding of the radiotracer (28% at 1h post incubation) in HT-29 cells and in-vivo data exhibited an uptake of 7.1 % ID/gm at 24h post-injection in HT-29 tumors indicating high affinity of the radiotracer towards FAP. The preparation retained its biological integrity (BET and ST) and RCP >98% up to a period of 168h enabling its transport to distant nuclear medicine centers for its end utilization in cancer patients. Conclusions: A protocol for multiple patient dose formulation of [177Lu]Lu-FAPI-46 was successfully developed and established. Promising pre-clinical results demonstrates the potential clinical therapeutic application of [177Lu]Lu-FAPI-46for TRT of FAP overexpressed metastatic solid tumors in patients.
Therapy 8: Loading of 177Lu-PSMA-617 on biodegradable nanofiberous patch for the therapeutic purpose of residual tumours after resection – A novel radiopharmaceutical therapy system
Santosh Kumar Gupta, Ravi K. Chauhan, Priya Singh, Sanjeev K. Mahto
MPMMCC (A Unit of TMC) and IITBHU, Varanasi, Uttar Pradesh, India
Introduction: One of the leading causes of mortality globally is cancer. The foundation of today's cancer treatments are surgery, chemotherapy, and radiation. However, these methods suffer from a number of drawbacks, including surgical problems, systemic adverse effects of chemotherapy, and cancer recurrence. In order to successfully prevent recurrence, a unique controlled-release radiation delivery device for implantation after tumour excision is thus essential. Here, the nanofibrous fabricated was a blend of two different natural proteins: Soya Protein Isolate (SPI) and silk fibroin. These biocompatible and biodegradable nanofibers was prepared by electrospinning technique. In addition, 177Lu-PSMA-617 was loaded on nanofibers and these therapeutic radioisotopes loaded nanofibers had stability for approximately 28 days and exhibited a sustained release of radiation for at least 2 weeks, and were evaluated for implantation following tumour resection. The aim of this study was to encapsulate 177Lu-PSMA-617 and release of radiation from biodegradable nanofibers loaded with 177Lu-PSMA-617. Materials and Methods: We prepared a 177Lu-PSMA-617 loaded nanofibrous patch, assembled from biodegradable soya protein and silk fibroin. The produced nanofibers have a high porosity and high surface area-to-volume ratio that allow for drug loading, cell incorporation, migration, and proliferation and ample space for these processes. Nanofibers were prepared in three different ratios: Type-I SPI: SF; 75:25 (w/w), Type-II SPI: SF;50:50 (w/w), and Type-III SPI: SF;25:75 (w/w). 2mCi of 177Lu-PSMA-617 was added to each fibrous patch. Results: It was observed that type-I nanofiber delivered radiation a sustained and controlled manner in vitro. The slow, sustained delivery of radiation in vivo may increase the induction of apoptosis in residual tumor cells and inhibition of tumor angiogenesis. Conclusion: We concluded that 177Lu-PSMA-617 loaded with nanofibers could be introduced as a promising treatment for implantation upon post-surgery of the tumour. Animal studies will be evaluated in the next step of studies.
Therapy 9: Radioiodine (Iodine-131) loaded Biodegradable nanofibrous patch for the therapeutic purpose of residual tumors after resection – A novel radionuclide therapy system
Priya Singh, Ravi K Chauhan2, Dr. Santosh K Gupta2*, Dr. Sanjeev K Mahto1*
Indian Institute of Technology(BHU) and Nuclear Medicine Mahamana Pt. Madan Mohan Malviya Cancer Centre Banaras Hindu University
Introduction: One of the leading causes of mortality globally is cancer. The foundation of today's cancer treatments are surgery, chemotherapy, and radiation. However, these methods suffer from a number of drawbacks, including surgical problems, systemic adverse effects of chemotherapy, and cancer recurrence. In order to successfully prevent recurrence, a unique controlled-release radiation delivery device for implantation after tumour excision is thus essential. Here, the fabricated nanofibrous patch contained blends of two different natural proteins: soya protein isolate (SPI) and silk fibroin. These biocompatible and biodegradable nanofibers were prepared by electrospinning technique. In addition, radioiodine (Iodine-131) was loaded on nanofibers, and these therapeutic radioisotopes-loaded nanofibers had stability for approximately 30 days and exhibited a sustained release of radiation for at least 2 weeks, and were evaluated for implantation following tumour resection. The aim of this study was to encapsulate radioiodine (I-131) and release of radiation from biodegradable nanofibers loaded with radioiodine. Materials and Methods: We prepared a radioiodine (I-131) loaded nanofibrous patch, assembled from biodegradable soya protein and silk fibroin. The produced nanofibers have a high porosity and high surface area-to-volume ratio that allow for drug loading, cell incorporation, migration, and proliferation and ample space for these processes. Nanofibers were prepared in three different ratios: Type-I SPI: SF; 75:25 (w/w), Type-II SPI: SF;50:50 (w/w), and Type-III SPI: SF;25:75 (w/w). 2mCi of radioiodine was added to each fibrous patch. Results: It was observed that type-I nanofiber delivered radiation a sustained and controlled manner in vitro. The slow, sustained delivery of radiation in vivo may increase the induction of apoptosis in residual tumor cells and inhibition of tumor angiogenesis. Conclusion: We concluded that radioiodine (I-131) loaded with nanofibers could be introduced as a promising treatment for implantation upon post-surgery of the tumour. Animal studies will be evaluated in the next step of studies.
Therapy 10: To assess response in patients undergoing I-131 MIBG therapy for pheochromocytoma and paraganglioma – our experience (1994-2023)
Hanna Elizabeth Johnson, Saumya Sara Sunny, Julie Hephzibah
Department of Nuclear Medicine, Christian Medical College, Vellore, Tamil Nadu, India
Introduction: Pheochromocytomas and paragangliomas originate in the adrenal medulla and in the extra-adrenal ganglia respectively; and malignancy occurs in ~10% of pheochromocytomas and ~20-40% of paragangliomas. Symptoms are varied and are often related to an excessive and sudden secretion of catecholamines; of which hypertension is commonly the most life threatening. Functional imaging with I-131 MIBG scintigraphy is performed to determine the eligibility for I-131 MIBG therapy. Materials and Methods: A retrospective analysis of patients diagnosed with metastatic pheochromocytoma and metastatic paraganglioma who underwent I-131 MIBG therapy from 1994-2023, was conducted. Treatment response to I-131 MIBG therapy was assessed. A therapeutic dose of ~ 100mCi of I-131 MIBG was administered intravenously for patients with a positive diagnostic I-131 MIBG scan. All patients received adequate α and ß-adrenergic blockade prior to therapy. Thyroid blockade was done using oral potassium iodide. Results: A total of 92, I-131 MIBG scans were performed for patients with known / suspected pheochromocytoma and/or paraganglioma. Among these, 27 patients who had a positive I-131 MIBG scan underwent surgical resection and did not require further treatment with I-131 MIBG therapy; and 45 patients who underwent I-131 MIBG imaging for suspicious lesions were found to be negative. Of the 20 patients (9-Males and 11-females) who underwent I-131 MIBG therapy, 13 were diagnosed with metastatic pheochromocytoma and 7 were diagnosed with metastatic paraganglioma. Metastatic Sites: Eight had hepatic metastases, 11 had osseous metastases, 5 had lung metastases, 7 had lymph nodal metastases and one patient had metastasis to the urinary bladder. 18/20 patients underwent surgery at diagnosis. Additional new sites of metastases were noted in 7/20 patients in the post therapy scan.
No. of therapies:
| Number of therapies per patient | Number of patients |
|---|---|
| 1 | 3 |
| 2 | 7 |
| 3 | 3 |
| 4 | 3 |
| 5 | 3 |
| 6 | 1 |
Despite repeated therapies with I-131 MIBG, none of the patients had any severe side effects reported. Partial Responders: 11/20 patients had partial response which was defined as biochemical response with stable / decreasing intensity of lesions on I-131 MIBG imaging. 4/11 patients had complete resolution of symptoms and 7/11 had a decrease in symptoms. Disease Progression: 9/20 patients had progressive disease, of which 4/9 had biochemical progression alone and 5/9 had both biochemical and structural progression. Among these, 3/9 patients had symptomatic relief. Among the 20 patients who received I-131 MIBG therapy only one patient experienced severe vomiting as an immediate side effect post therapy, which was managed conservatively. Conclusion: I-131 MIBG therapy was useful in symptomatic relief in 70% of the patients.
55% patients had partial response to therapy
I-131 MIBG therapy is effective in preventing disease progression and reducing symptoms derived from hormonal abnormality and metastatic lesions
I-131 MIBG therapy is given at every six months interval which improved patient compliance to therapy and reduced the economic burden
Minimal / no adverse effects were noted despite repeated therapies
I-131 MIBG therapy is cost effective and is easily available in our country.
Therapy 11: Loading of 177Lu-DOTATATE on biodegradable nanofibrous patch for the therapeutic purpose of residual tumours after resection – A novel radionuclide therapy system
Ravi Kumar Chauhan, Priya Singh, Santosh K. Gupta, Sanjeev K. Mahto
Homi Bhabha Cancer Hospital (A Unit of TMC), Varanasi, Uttar Pradesh, India
Introduction: Post-surgery followed by radiotherapy, hormone, and chemotherapy, are the current mainstays for cancer treatment. However, these strategies have systemic toxicities and limited treatment outcomes. Hence, there is a crucial need for a novel controlled release delivery system of radiation for implantation following tumour resection to effectively prevent recurrence. Here, the nanofibrous fabricated was a blend of two different natural proteins: Soya Protein Isolate (SPI) and silk fibroin. These biocompatible and biodegradable nanofibers was prepared by electrospinning technique. In addition, 177Lu-DOTATATE was loaded on nanofibers and these therapeutic radioisotopes loaded nanofibers had stability for approximately 28 days and exhibited a sustained release of radiation for at least 2 weeks, and were evaluated for implantation following tumour resection. The aim of this study was to encapsulate 177Lu-DOTATATE and release of radiation from biodegradable nanofibers loaded with 177Lu-DOTATATE. Materials and Methods: We prepared a 177Lu-DOTATATE loaded nanofibrous patch, assembled from biodegradable soya protein and silk fibroin. The produced nanofibers have a high porosity and high surface area-to-volume ratio that allow for drug loading, cell incorporation, migration, and proliferation and ample space for these processes. Nanofibers were prepared in three different ratios: Type-I SPI: SF; 75:25 (w/w), Type-II SPI: SF;50:50 (w/w), and Type-III SPI: SF;25:75 (w/w). 2mCi of 177Lu-DOTATATE was added to each fibrous patch. Results: It was observed that type-I nanofiber delivered radiation a sustained and controlled manner in vitro. The slow, sustained delivery of radiation in vivo may increase the induction of apoptosis in residual tumor cells and inhibition of tumor angiogenesis. Conclusion: We concluded that 177Lu-DOTATATE loaded with nanofibers could be introduced as a promising treatment for implantation upon post-surgery of the tumour. Animal studies will be evaluated in the next step of studies.
Therapy 12: Noninvasive treatment of recalcitrant keloids with contact brachytherapy using customized Yttrium-90 skin patch and its effectiveness: A pilot study
S. Sai Kishore, Nandini Pandit, V. C. Sunitha, Rashmi, N. Hariharasudhan
Department of Nuclear Medicine, JIPMER, Pondicherry, India
Introduction: The keloids are benign dermal fibroproliferative tumours. There are multiple treatment modalities for keloids like intralesional or topical steroids, cryotherapy, surgical excision, radiotherapy, and laser therapy in clinical practice with variable success rates. Recurrence rates are the main problems in many treatment modalities. Some of the keloids may go unresponsive or recurred multiple times on the standard routine treatment. These keloids are referred to as Recalcitrant keloids. We have analysed the effect of the Y-90 skin patch on recalcitrant keloids in the Indian population. Materials and Methods: 1 mCi of Y-90 skin patch was applied locally on the lesion for 3 hours. Then the patients were followed up at 2 months, 4 months and 6 months intervals. On each follow-up, visual assessment of the lesion, high resolution USG were done for assessing the change in the thickness (depth) of the lesion. VAS score of pain and pruritis were also noted in all patients. Sample size (lesion no): 28. Results: We found that there is reduction in the thickness of recalcitrant keloids after applying 1 mCi of Y-90 skin patch in this single-arm trial. There is no significant decrease in the pruritis upon patch application over 6 months. The pain could not be commented upon because many patients had no pain during the baseline evaluation. Few patients/lesions (whose lesions are very bulky) had a recurrence over the follow up period of 6 months. Side effect profile: Most patients had initial skin ulcer and subsequently developed into hypopigmentation. No other side effects are noted. Conclusion: The decrease in thickness implies the effect of the Y-90 skin patch on recalcitrant keloids. There was an optimum change of thickness from baseline with 6 months follow-up. Few recurrence up to 6 months was observed during the follow-up. All the patients experienced subjective symptomatic relief in pruritis after the patch therapy. Therefore Y-90 skin patch is a cheap, non-invasive, effective treatment for recalcitrant keloids.
Therapy 13: Single time point SPECT data analysis using Q-Metrix reconstruction approach for response assessment to 177Lu-DOTATATE therapy in metastatic NET patients – A pilot study
Kirti Dhingra, Komalpreet Kaur, Bhagwant Rai Mittal, Baljinder Singh
Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Introduction: The Q-Metrix incorporated into the single time point SPECT/CT iterative reconstruction algorithm was used to estimate the change in the tumor volume and uptake values as parameters of response assessment to the subsequent 177Lu-DOTATATE therapy in metastatic NET patients. Materials and Methods: Seven patients (4M,3F with mean age 54.85 ± 8.37 years) with histopathological evidence of GEP-NET, considered for 177Lu-DOTATATE therapy were recruited in this pilot study. 68Ga-DOTATOC PET/CT imaging was performed in all patients prior to DOTATATE therapy. The patients were administered i.v. with 7.4 GBq dose of 177Lu-DOTATATE with adequate kidney protection by amino acid infusion. The whole-body scanning was done (256×1024 matrix) at 24h using dual head gamma camera (Discovery, 670 DR, GE Healthcare), peaked at 113keV and 208keV and coupled to medium energy collimator. Thereafter, the regional SPECT/CT acquisition (of abdominal region and region/s showing increased tracer avid lesions) was performed (in 64×64 matrix; 60 projections; 15 sec/projection). The SPECT/CT data were reconstructed using OSEM reconstruction method (4 iterations, 10 subsets) which also included for AC/SC/RR. The volume of interest (VOI) was automatically segmented using NM threshold fused SPECT/CT images on the primary and metastatic tumor sites. The tumor volume, absolute tracer concentration and % injected activity were estimated quantitatively using Q-Metrix software. This Metrix enables the display of lesions and organs in activity concentration using SPECT/CT images by incorporating system 177Lu sensitivity, injected dose information, scan and patient (height & weight) parameters. All these quantitative parameters were also evaluated after the 2nd cycle of therapy (after 6 months) for response assessment. Results: A total of 34 tracer (177Lu-DOTATATE) avid lesions (range 3-8 lesions per patient) identified on whole body and SPECT/CT images and matched on the first and second therapy images were analyzed for quantitative change (if any) in tumor volume and tracer uptake using Q-Metrix approach. In patients’ wise lesions analysis, a decrease in both lesion volume and tracer uptake was noted on the second cycle of therapy as compared to the first therapy. The absolute tumor volume and tracer uptake change ranged from 1.06-23.3 mL and 2.43-18.6% respectively. On the other hand, the mean percent change in tumor volume and tracer uptake ranged between 19.7%-67.7% and 8.25-92.50% respectively. A significant correlation was observed for absolute tumor volume (r = 0.990; p = 0.05) and tracer uptake (r = 0.922; p = 0.05) for the corresponding tumor lesions evaluated after the first and second therapy cycle. Likewise, a significant correlation was also seen between absolute tumor volume and tracer uptake for the first cycle (r = 0.951; p = 0.05) and the second cycle (r = 0.963; p = 0.05) respectively. Conclusion: This pilot study thus highlights that Q-Metrix derived tumor volume and tracer lesions’ uptake using a single time point SPECT/CT data are sensitive indicators for quantifying the response to the subsequent 177Lu-DOTATATE therapy in NET patients. The robustness of this approach, however, needs validation in a larger number of patients.
Therapy 14: Performance evaluation of 224Ra/212Pb generators used for 212Pb -peptide preparations as a TAT agent for clinical use
Navneet Singh, N. Rana, P. Thakral, Jyotsna, D. Khichi, J. Gupta, M. Koley, S. S. Das, D. Malik, I. B. Sen
Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurugram, Haryana, India
Introduction: Alpha-emitting radionuclides have gained considerable attention as payloads for cancer targeting molecules due to their high cytotoxicity. One attractive radionuclide for this purpose is Pb-212, which by itself is a β-emitter, but acts as an in vivo generator for its short-lived α-emitting daughters. Half-life(t1/2-10hrs) of Pb-212, matches the pharmacokinetic properties of peptides and thus, facilitates isotope utilization as a therapeutic agent for targeted alpha therapy. We hereby, report the usage of 224Ra/212Pb generator system with an aim to evaluate the feasibility as well as the performance of 224Ra/212Pb generators to be used for radiosynthesis of 212Pb-peptides for Targeted alpha therapy. Materials and Methods: The 224Ra/212Pb (VMT-α-GEN) generator was procured from Viewpoint Molecular Targeting™. The generator used was a column-based generator that employed 31.25mCi (1156.25MBq) of Radium-224 (Ra-224) adsorbed onto a cation exchange resin. The entire system was housed in a fume hood with lead shielded environment (4–6″ Pb). Pb212 was extracted from the generator by the passage of 4ml 2M HCl through the column at a speed of 0.5ml/min under a fumehood with a charcoal filter in the elution vial to absorb the short lived Rn-220 (t1/2-55secs). The eluted Pb-212 was then transferred to the Pb resin catridge preconditioned with 1ml 2M HCl, to remove the impurities. Pb-212 was subsequently eluted in acetate form using 2mL of 1M sodium acetate buffer (pH = 6) which was directly used for radiolabeling reactions. The generator had a shelf life of 1 week and was be eluted 2-3 times at an interval of 24 hrs. Results: 14 generators (31.25mCi of Ra-224 loaded) were used over a period of 10 months. All the generators were eluted once, nine generators were eluted twice and only four generators were eluted thrice with an interval of 24 hrs between subsequent elution and a 27 runs of radiosynthesis with peptide were done. The mean average time elapsed from the day of manufacture of the generator to the day of first elution was 120hrs. The average yield of Pb-212 along with daughters from the generator in 1st elution was noted to be 67.6% which mounted to 73.5% in the 2nd elution. Mean yield of Pb-212 after purification through Pb-resin was 35% for all the elutions however, the Pb-212 activity increased upto 3 hrs until the equilibrium with Ra-224 was reached. The purification resulted in the successful removal of all the daughters and no Ra-224 breakthough was noted. The purified Pb-212 was used for the labeling with peptide and the final yield of the radiolabelled product obtained was 91%. The RCP of radiopharmaceuticals as determined by thin layer chromatography was 98 ± 0.22%. Conclusion: The generator represents a feasible, straight forward and promising method for efficient production of Pb-212 without the use of sophisticated machinery, time-consuming processes, or hazardous chemicals which can be efficiently utilized for further radiolabeling with peptides as targeted alpha therapy agent for clinical use.
Therapy 15: Radiation synovectomy in haemophilic arthropathy
Krishna Mundada, Shwetal Pawar, C. S. Chandrakala, Shubnato Mohanty, Kirti Patil
Department of Nuclear Medicine, Seth G.S. Medical College and Dr. R.N. Cooper Hospital, Mumbai, Maharashtra, India
Introduction: Hemophilic arthropathy is a degenerative condition caused due to deposition of hemosiderin followed by a cascade of inflammatory changes in synovial joints. Radiation synovectomy or radionuclide synovectomy (RS) is a well established procedure for the treatment of the condition. It is shown to cause necrosis of vessels and pain fibers in hypertrophied synovial membranes with reduction in recurrent inflammation. While the procedure has proven benefits such as reduction in recurrent swelling, re-bleeding and pain alleviation; very few studies have correlated synovial membrane measurements on MRI, type of synovial joint being treated to the overall subjective as well as objective outcomes on followups. This becomes even more important in an Indian scenario, given the limited literature targeting the population. The purpose of the study was to analyze subjective improvement and its correlation to MRI findings, the extent of damage to the joint and requirement of deficient factor. Materials and Methods: 80 hemophiliac arthropathy patients with recurrent joint bleeding were assessed retrospectively who underwent radiation synovectomy using Yttrium-90 hydroxyapetite (Y-90 HA) mean dose of 5mCi for knee joint and Lutetium-177 hydroxyapetite (Lu-177 HA) mean dose of 5 mCi per joint during last 1 year. The severity of haemophilic arthritis was scaled as mild, moderate and severe based on occupational therapy assessment, and changes in cartilage reported as destruction, subchondral cystic/erosive. The pain was scaled using Wong-Bakers rating scale (pre and post procedure) and improvement in range of movement specific to joint action, along with requirement of factor and rebleeding. Synovial thickness on MRI was recorded at baseline and 3-6 mns post-procedure. Results: 38/46 (82.6%) knee joints were injected with Y-90 HA (Y Knee group) while 8/46 (17.3%) were injected with Lu-177 HA (Lu Knee group). 22/46(47.8%) patients were followed up in which 19/22 (86.36%) showed significant (p < 0.001) reduction in bleeding episodes, while 3/22 (13.63%) patients reported no change. On average, patients in the knee group ranked the pain to be 6.67/10 which improved to an average 2.65/10 after the procedure. 15/20 (75%) patients were injected with Y-90 HA (Y elbow group) while 5/20 25% were injected with Lu-177 HA (Lu elbow group) in the elbow joint. Follow up of 7 patients from Y-90 elbow group was available with an improvement in pain by an average 7.85 to 1. The bleeding episodes were down from 3.35/mn to no reported episodes in 3 patients and average of 0.16/mn (1-2/yr) in others. The Ankle group had 14 patients with significant reduction in both pain from 7.5/10 to 3/10. All joints showed reduction in synovial thickness on MRI of >1mm in each pocket post-procedure. Conclusion: Radiation synovectomy using Y-90 HA and Lu-177 HA showed improvement in the joint function, reduction in pain and number of bleeding episodes and subsequent deficient factor requirement and synovial thickness
Therapy 16: Serum thyroglobulin as a prognostic marker for remnant ablation efficacy after total thyroidectomy in thyroid cancer
Manish Ora, Aftab Nazar Hasan, Amitabh Arya, Sukanta Barai, P. K. Pradhan, Sanjay Gambhir
Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: Differentiated thyroid cancer (DTC) treatment is total thyroidectomy, followed by 131I remnant ablation (RIA), depending upon the stage and risk factors. After RIA, the patient is followed up with stimulated serum thyroglobulin (Tg) and antithyroglobulin antibody (ATg) levels with or without a diagnostic whole-body scan (WBS) to verify the absence of disease. RAI eliminates remaining thyroid tissue, facilitating the detection of recurrent disease and initial staging through Tg and RAI scans. This study aimed to evaluate the success rate of remnant ablation using radioiodine in patients with thyroid cancer. Materials and Methods: This study aimed to evaluate the success rate of remnant ablation using radioiodine in DTC. A retrospective analysis was conducted on a cohort of patients who underwent total thyroidectomy between January 2014 and December 2017 at a tertiary care hospital. Patients were included based on specific criteria of DTC with lymph nodal or distant metastases on the RAI scan. All patients have a minimum of 2 years follow-up. A successful ablation was defined as a negative RAI scan and Tg <0.2 ng/mL. Exclusion criteria involved patients with elevated ATg or poorly differentiated variants of papillary thyroid carcinoma. Results: The study included 383 patients. The age at diagnosis was 37.8 ± 12.9 years. The patient received RAI at 3.9 ± 3.1 months. The baseline Tg and ATg were 29.4 ± 66.5 ng/ml and 95.2 ± 341.1 IU/dl, respectively. A total of 251 patients had successful ablation in a single dose of RIA (70.3 ± 33.6 mCi). There was a significant difference in the successful remnant ablation between a baseline S Tg level <12.3 and more than 12.3 (84.1 % vs 21.2 %, p = 0.001). Conclusion: A single dose of the RAI successfully ablates two-thirds of the patients. The baseline serum Tg (<12.3) remains an important marker for predicting the success of the RAI. It is a simple and robust marker for prognosticating ablation in the DTC.
Therapy 17: Auger electron-based therapy in glioblastoma multiforme with 64CuCl2: An initial experience
Nidhi Singh Kushwaha, Md. Faheem, Vaibahv Pandey, Richa Maurya, Manish Dixit, Manish Ora, Sarita Kumari, Sanjay Gambhir
Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: Innovative therapeutic strategies are imperative in the realm of cancer treatment, especially in Glioblastoma multiforme (GBM), a high-grade brain tumour. Based on the evidence that the human copper transporter1(CTR1) is over-expressed in GBM, previous works have consistently demonstrated that radioactive copper-64 is an authentic tracer for in vivo characterization of copper metabolism in neoplastic tissues. Radioactive Copper 64 produced in Cyclotron and purified as [64Cu]CuCl2, a salt of copper, emits gamma rays and Auger electron and has been demonstrated to cumulate in replicating cancer cells, thus making useful for imaging via Positron emission tomography (PET) and also delivering high energy Auger radiation(~80 KeV) within a sub-cellular range (theranostics). It accumulates preferentially in cancer cell nuclei, enabling targeted therapy. The unique triple decay pathways (positron emission, electron capture, beta decay) allow versatile production methods, aiding PET imaging and radionuclide therapy. This breakthrough paves the way for novel theranostic approaches, holding significant clinical potential in the fight against cancer. Materials and Methods: The 64Cu was produced via nuclear reaction 64Ni(p,n)64Cu as [64Cu]CuCl2 as per the literature procedure. The quality control (QC) was performed and doses were administered in 0.9% isotonic saline solution with pH of 6-7. Till date, 7 patients (4 males and 3 females) having f-MRI and standard biochemical test were enrolled with confirmation of GBM (Grade III/IV) of age groups 20-50. Patients were randomly injected [64Cu]CuCl2(5,1 0 and 20 mCi) intravenously. PET images of the whole body were obtained in 3D mode, with an acquisition time of 3 minutes per bed position and acquired at 1, 3 and 24 hours post-injection. These patients are under follow-up after 3 months through MRI, [18F]FDG PET /CT scan and the standard biochemical tests (such as LFT and KFT) were analysed after 3 weeks as the follow-up. Standardized uptake values (SUVs) used for tracer pharmacokinetics. Results: The typical yields for 64Cu productions are in the 0.2-0.6 mCi/µA h range. The tracer uptake in the patients was observed which gradually increased with respect to time in most cases. It retained even at 24 hours of study and tumor to background ratio (TBR) increased at 24 hours. The SUVmax of five patients exhibited a narrow spectrum, ranging from 3.51 to 3.92 whereas in 2 patients it was notably lower at 1.12. Analysis after 3 hours later revealed a notable increase to a range of 3.70 to 3.9. Furthermore, after 24 hours, SUVmax values fluctuated, ranging between 1.8 to 5.25. The biochemical tests showed stable results in most patients post 3 weeks. Conclusion: [64Cu]CuCl2 is a well-tolerated radiotracer with reasonably favourable dosimetric properties, showing selective uptake in tumour areas with visible contrast enhancement and necrosis, thus suggesting that blood–brain barrier damage is a pre-requisite for its distribution to the intracranial structures. Moreover, tracer uptake showed an accumulating trend over time. The Auger therapy brings up the option of administering additive, very localized radiotherapy to metabolically active target tumour volume, which is a highly appealing. The detailed results are still awaiting.
Category: Thyroidology
Thyroidology 1: The effect of heterophilic antibody interference in thyroglobulin measurement in differentiated thyroid cancer patients: Clinical implications and detection algorithm
Smt. Chandrakala Gholve, Savita Kulkarni, Shri. Nawab Singh Baghel
Radiation Medicine Centre, BARC, Mumbai, Maharashtra, India
Introduction: Serum thyroglobulin (Tg) is a biochemical tumor marker used in the follow-up of differentiated thyroid cancer (DTC) patients. However, interferences resulting due to anti-Tg autoantibodies (TgAb), heterophile antibodies (HAb) and ‘hook-effect’ may limit the clinical use of Tg regardless of kind of Tg assay used. HAb consists of natural antibodies and autoantibodies that are polyreactive against heterogeneous, poorly defined antigens exhibiting low affinity and weak binding. The prevalence of HAb in the population is 30–40% caused due to infection, vaccination, ingesting animal antigens, keeping pets, and even blood transfusion. There is no general algorithm for detecting interferences. Our study aimed at finding out the effect of HAb interference in Tg measurement in the serum samples of DTC patients. Materials and Methods: The study comprised DTC patients (n = 99) approaching RMC OPD for follow-up. The Tg measurements were performed on the RIA autoanalyzer using an in-house developed immunoradiometric assay (IRMA) kit which is being used routinely in our laboratory. The indirect ‘Tg recovery’ approach was used to detect TgAb interference with additional application in the detection of the ‘hook effect’ where the suspected sample was diluted (1:10) and reanalyzed. A unique formulation (cocktail) of non-immune immunoglobulin, including pooled globulin from animal species was used for preparing in-house heterophile blocking tubes (HBT) which were used for capturing HAb in the sample. The Tg estimation was performed on both the HBT-treated and untreated samples (n = 99). Results: Tg recovery values were used for identifying the interferences in complement with the Tg values. Tg IRMA assay results in the samples were reported as TgAb negative in 89 (89.8%), positive in 3 (3%), positive/negative (grey zone) in 1 (1%). The hook effect was observed in 6 (6%) samples which were reported as >300 ng/ml (working assay range up to 300 ng/ml) after re-assaying the diluted sample. The heterophile interference was detected in 1 (1%) sample presenting a false-positive result when compared with the Tg recovery value. But nevertheless, reduced by 30% post-HBT treatment. The Tg values before and after HBT treatment were 88 ng/ml and 69 ng/ml respectively in this sample. Conclusion: Despite the use of advanced laboratory equipment, HAb can still cause false high Tg measurements, especially in the immunometric assay format. Interfering antibodies are highly heterogeneous in their mechanisms of interference and vary in affinity, avidity and binding sites, even within a single assay. Efforts are now being directed toward detecting this interference, but nonetheless, most of them are impractical and therefore, cannot be practiced routinely. Hence, at the laboratory level surveillance in the form of detection and classification of interference and their elimination is obligatory. Our study showed that the interference of HAb in the Tg assay is low. Further, analytical errors can be avoided with utmost care and effective communication between clinicians and laboratory specialists. Clinicians should be aware of possible HAb interference, especially if there is any inconsistency between the clinical status of the patient and the laboratory result which may prevent patients from being misdiagnosed and/or exposed to treatment.
Thyroidology 2: Evaluation of frequency of micronuclei, nucleoplasmic buds and bridges in the peripheral blood lymphocytes of patients receiving therapeutic 131I exposure
U. S. Bhartiya, Kamaldeep, N. Bhat, G. Malhotra, A. Chaur, S. Kulkarni1, N. Singh
Radiation Medicine Centre, BARC, Mumbai, Maharashtra, India
Introduction: Internal administration of 131I therapy to patients with differentiated thyroid carcinoma has been a standard mode of practice for the ablation of the remnant thyroid tissue. As these patients are in a hypothyroid state due to withdrawal of thyroxine hormone treatment, renal clearance of the 131I is reduced and it's likely that it will get retained in the body for a longer period, which may increase the extent of whole body 131I exposure. Standard physical dosimetry techniques are used for assessing therapeutic radioiodine exposure using external devices. Currently, bone marrow dose predicted by these models are the limiting factor while deciding the activity to be administered to avoid excessive bone marrow damage. Even though they may be useful in routine clinical practice, they cannot assess the biological effects of therapeutic radiation exposure at the cellular levels. The study was planned to observe the effect of single therapeutic oral dose of 131I on DNA anomalies in peripheral blood lymphocytes (PBLs) i.e., micronuclei (MN), nucleoplasmic buds (NBUDS) and nucleoplasmic bridges (NBR) and evaluate its utility as a biological dosimeter to assess the whole body dose other than target organ i.e., thyroid. Materials and Methods: Blood samples were collected from healthy volunteers (n = 9), forming control group and thyroid cancer patients (n = 18) before and 72 hrs after therapeutic 131I exposure (5.7 ± 2.1 GBq). The samples were processed by standard Cytokinesis block micronuclei assay protocol. The presence of MN, NBR and NBUDS/1000 binucleate (BN) PBLs was scored. Results: The MN frequency in untreated thyroid cancer patients is found to be significantly higher as compared to controls in study group (5.5 ± 2.3, MN 1000 BN Cells v/s 8.7 ± 3..7 MN/1000 BN Cells) (p = 0.026), but NBUDS and NBR frequency did not alter significantly. PBL MN frequency, NBUDS (Pre7.4 ± 5.3 Post 11.9 ± 7.2) and NBR (Pre 5.7 ± 4.4, Post 14.4 ± 8.1) were found to be raised significantly in patients’ samples after receiving therapeutic 131I exposure. (p < 0.0001, Pre vs Post 131 I exposure). The observed MN, NBUD and NBR frequency poorly correlated with administered 131I doses as they may not directly translate into peripheral blood and/or bone marrow doses. Conclusion: Frequency of MN, NBR, NBUD index in PBL can be explored as bio-dosimeters for estimation of absorbed dose post 131I therapy. The dose estimates by physical and biological dosimetry should be correlated and can be used for better understanding of body burden estimation associated with repeated therapeutic 131I exposure.
Thyroidology 3: Exploring the possible correlation between TC-99m thyroid uptake and 24 Hr. I-131 uptake
Manisha Pradhan, Satyawati Deswal, A. K. Shukla
Department of Nuclear Medicine, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Introduction: The alteration in thyroid hormonal profile results into host of disorders including Graves’ disease which is an autoimmune disorder caused by excess production of thyroid hormones and accounts for about (50-80) % of all cases of thyrotoxicosis. The present study was conducted to ascertain a correlation between thyroid uptake of Tc-99m and I-131 in 20 cases of Graves’ disease. Materials and Methods: Retrospectively performed thyroid scan by using 99mTc (3-5) mCi under DISCOVERY NM/CT 670SERIES SPECT/CT and thyroid uptake study using I-131 50uCi capsule by CAPINTEC 4000e thyroid probe and a leucite neck phantom in 20 patients of Graves’ disease reporting to the department of Nuclear Medicine, DR RMLIMS, Lucknow. Studies were performed 20 minutes after intravenous injection of 99mTc-pertechnetate and images were obtained on dual head SPECT gamma camera. The ROI were drawn on thyroid gland and background to compute the no. of counts. After applying decay correction, the % uptake was calculated by:
% uptake = [(thyroid count - background count)/ (pre-injection syringe count-post injection syringe count)] × 100%
For thyroid uptake using I-131, the dose was administered orally and scintillation probe was used for thyroid uptake measurements at 25 cm at 0 hour, 4 hrs., and 24 hrs. respectively.
The I-131 Uptake % = (Neck count – thigh counts)/ (standard counts background) *100.
Results: The Tc-99m uptake was observed to be ranging from 2.10% to 43% whereas I-131 uptake ranges from 11.8% to 107.70%. The coefficient of correlation, r indicated no correlation between the two studies suggesting there is no linear correlation or link between the variables. Conclusion: The study shows negative correlation between Tc99m scan and 24 hr. I-131 uptake values. However, it would be appropriate to undertake such a study with larger no. of cases to predict whether any of these two can be used in an alternative manner as a method for deciding therapeutic doses in cases of Graves’ disease.
Thyroidology 4: 68Ga-NODAGA-RGD PET-CT imaging in patients of thyroglobulin elevated negative 131I scintigraphy carcinoma thyroid and anaplastic thyroid carcinoma
Abhay Gondhane, Priyanka Verma, Ashok R. Chandak, Sandip Basu
Radiation Medicine Centre, Mumbai, Maharashtra, India
Introduction: One of the most challenging clinical situations in patients with DTC is TENIS. The treatment approaches include redifferentiation therapy, molecular targeted therapy with TKI and cyclooxygenase 2 inhibitors, chemotherapy, and PRRT. This study aimed to demonstrate the uptake/expression of RGD binding integrins in TENIS and ATC cases using 68Ga-NODAGA-RGD PET-CT. Materials and Methods: This was a prospective study of 30 patients performed 2022 to 2023. The study was approved by the Institutional Scientific and Medical Ethics Committee. The inclusion criteria were proven cases of TENIS and histopathologically proven ATC. Results: In this study, a total of 30 patients (11 females and 19 males) were enrolled, with ages ranging from 25 to 75 years. In 18F-FDG-PET-CT, uptake was seen in 182/200 (91%) lesions. Soft tissue, lung, and skeletal metastatic lesions were seen in 47/47 (100%), 117/130 (90%), and 18/23 (78.26%) respectively. 68Ga-NODAGA-RGD-PET-CT, uptake was noted in 110/200 (55%) lesions. Soft tissue, lung, and skeletal metastatic lesions were seen 25/47 (53.19%), 66/130 (51.53%), and 19/23 (82.60%) respectively. 68Ga-NODAGA-RGD-PET-CT was positive for the disease in 21/30 (70%) patients and negative in 9/30 (30 %) patients. All 21 patients were true positives (TP), 2/9 were true negatives (TN) and 7/9 were false negatives (FN). There were no false positives (FP) on 68Ga-NODAGA-RGD-PET-CT. Lesion-wise, the overall sensitivity and specificity of 68Ga-NODAGA-RGD-PET-CT were 75% and 100% respectively.18F-FDG-PET-CT was positive for the disease in 26/30 (86.66%) patients and negative in 4/30 (13.33%) patients. All 26 patients were true positives (TP), 2/4 was true negatives (TN) and 2/4 was false negatives (FN). There were no false positives (FP) on 18F-FDG PET-CT. The overall sensitivity and specificity of 18F-FDG-PET-CT was 92.86% and 100% respectively. A 4-point visual grading system was done to estimate the degree of radiotracer avidity, inspired by Krenning's score; on 68Ga-NODAGA-RGD-PET-CT, we observed 14/200(7%) lesions showing Grade I uptake, 49/200(24.5%) lesions show grade II uptake, 17/200(8.5 %) lesions show grade III uptake and 40/200(20%) lesions show grade IV uptake. Conclusion: The results suggest that RGD-binding integrin is expressed in a sizeable fraction of metastatic lesions of TENIS cases and anaplastic carcinoma of the thyroid and 68Ga-NODAGA-RGD-PET-CT demonstrates expression in the various sites of metastasis in TENIS and anaplastic carcinoma. Out of soft tissue lesions, lung lesions, and bone lesions, bone lesions showed more RGD affinity than other sites. The result implies potential RGD–based therapy options for the positive patients with high uptake. The patients with substantial RGD uptake based on 4-point visual grading system may be potential targets for such a therapy. Many subcentimeter sized soft tissue lesions and lung nodules show low-grade or no uptake of RGD as compared to 18F-FDG PET-CT, who are not candidates for this therapy. Further dosimetric studies may be worthwhile in this regard.
Thyroidology 5: Iodine-131-MIBG therapy for medullary thyroid cancer in a tertiary care hospital in India: 28 years’ experience
J. Benjamin, J. Hephzibah, S. Sunny
Department of Nuclear Medicine, Christian Medical College, Vellore, Tamil Nadu, India
Introduction: Medullary thyroid cancer (MTC) is a rare neuroendocrine slow growing tumour that produces calcitonin from parafollicular cells. However, metastasis to regional lymph nodes is frequently notes at the time of diagnosis. Wide-ranging careful surgery is the only remedial option for localized MTC. Metaiodobenzylguanidine (mIBG) is structurally similar to the neurotransmitter norepinephrine and specifically targets neuroendocrine cells. In this context we wanted to assess our own experience of treating MTC patients with 131I-mIBG therapy and to assess if there was any role of the same in the current scenario. Materials and Methods: Retrospective study done in patients who underwent 131I-mIBG therapy in our institution between 1990-2023. As per our data, over 2000 studies who had I-131mIBG scans for various indications in our department, there were 15 patients (12 male, 3 female) with MTC who were eligible and underwent 131I-mIBG therapy in this period. Their age at diagnosis was ranging from 10-64 (Median age: 41) years. 131I-mIBG Imaging: Planar whole body images were obtained 24 h, 48 h, and 72 h after injection of 37-40 MBq 131I-MIBG. Serum calcitonin which is a well-established sensitive and specific marker for MTC, was noted in the clinical follow up of these patients. 131I-mIBG treatment: The patients were infused with 131I-mIBG (dose-adjusted) in 100 ml 0.9% sodium chloride solution through an intravenous line using a syringe pump over a period of 3 hours (doses ranging from 30.5 to 120 mCi). Results: Twenty three 131I-mIBG therapy doses were administered (range 1-4 doses/pt). The follow-up period ranged from 1-14 years (Median 3.5 years). Their initial serum calcitonin levels ranged from 2.75-46200 pg/ml in the available data. On their follow up, the calcitonin levels remained stable in 8/13 patients and progressed in 5/13. The data was unavailable for 2 patients. Only one patient is on follow up till date, 4 succumbed to the disease and the rest were lost to follow up. CEA was done in 5/15 and was found to be increasing as the disease progressed. Initially the mIBG scan was positive for metastases in 10/15 of them (liver mets – 5, lung mets – 4, mediastinal mets - 1), 2/15 residual, 2/15 initially negative and later on positive, and 1/15 the data was not available. On follow up with repeat mIBG scans, 3/12 alone showed regression whereas the rest showed progression and had other adjuvant therapies like PRRT, TKI's, XBRT which are comparatively expensive with significant side-effects. There were no reported side effects from the data available. Conclusion: The treatment with 131I-MIBG is well tolerated and may improve the condition of patients with metastatic MTC symptomatically. In a resource limited setting, 131I-mIBG therapy can be considered as a cheaper alternative for disease control. Further multicentric trials with larger sample may throw more light on management of MTC; as there are very few centres in India who have had the experience of treating MTC patients with 131I-mIBG therapy.
Thyroidology 6: Assessment of surface contamination in the scan room by Iodine-131 in routine high dose ablation therapy scans: A departmental survey
Ajay Kumar, A. Kumar, K. Kaur, M. Kumar, A. Sood, B. R. Mittal
Department of Nuclear Medicine, JIPMER, Pondicherry, India
Introduction: High-dose radioiodine ablation/therapy using I-131 is preferred and effective treatment option for patients with thyroid cancer after thyroidectomy. I-131 is used for diagnostic and therapeutic purposes. Administration of high-dose I-131 (100-150 mCi) is done on IPD basis. Since major route of I-131excretion is through gastrointestinal and urinary route with minimal excretion through sweat, saliva and breath patient's isolation protocol is followed and discharged at exposure rate less than 5µsv/hr at 1m distance. All patients receive instruction intended to reduce the spread of radioactive contamination to others living with or coming in close contact after their discharge. The aim of this study was to check the level of surface contamination in the high workflow department during post-ablation therapy scan that could be spread via perspiration specially while touching the handles and door knobs. Materials and Methods: A total of 20 patients (10 women, mean age 40 ± 20 years; range 14-65) were prospectively included in this study. Two groups of patients i.e one group undergoing post-therapy scan (group A) and other undergoing pre-therapy diagnostic scans (group B) were studied. Exposure rate for both the groups were measured using GM based survey meter (RAM GAM 1). In order to measure I-131 excreted in sweat which may result into surface contamination, sweat sample from palms of the patients were collected. The patients were asked to wear glove in one hand and squeeze a stress ball for 50-100 times and then sweat sample was taken from active palm using a wet swab. The swabs taken after the procedure were measured using well counter. Results: Exposure rates for patients undergoing post-therapy (group A) and pre-therapy diagnostic (group B) scans were measured at 1m distance using GM based survey meter and were found to be within limits. The mean exposure rate recorded was 0.6 and 0.1 mR/hr for group A and group B respectively. Sweat samples of palms were measured for both the patient groups and the mean surface contamination was found to be 69 dpm/25cm2 and 23dpm//25cm2 which equates to 1.15 Bq/cm2 and 0.38 Bq/cm2 for post-therapy and diagnostic group respectively. The mean surface contamination on door handles was found to be 1 dpm/25cm2 and 1.66 dpm/25cm2 which equates to 0.016 Bq/cm2 and 0.027 Bq/cm2 in the scan room at the beginning and end of the day. Conclusion: We found significant levels of I-131 activity in perspiration in thyroid cancer patients undergoing diagnostic and therapeutic scans done with I-131 during their departmental visit. The surface contamination with I-131 in our department was found to be well within limits as the optimum level for removable contamination is 220 dpm/100cm2 in open areas and 2200 dpm/100cm2 in restricted zones, which equates to 0.36 Bq/cm2. The relative high skin contamination found during the scans emphasizes the need to follow proper techniques to prevent significant transfer of radioactive iodine to their family and occupational workers in high workload departments.
Thyroidology 7: To evaluate the diagnostic utility of 68Ga-Pentixafor PET/CT in radioiodine refractory thyroid cancer patients: Preliminary results
Muazzam Nayeem, Ankit Watts, Sanjay Badada, Harneet Kaur, Baljinder Singh, B. R. Mittal
Department of Nuclear Medicine, PGIMER, Chandigarh, India
Introduction: The undifferentiated radioiodine refractory thyroid cancers pose a challenge with conventional radioiodine therapy. Though, this fraction (5.0-15%) of thyroid cancer often shows high avidity to 18F-FDG, but there are no radionuclide therapeutic options available currently. In this pilot study, we used 68Ga-Pentixafor PET/CT imaging to document the presence of CXCR4 receptors’ over-expression in a small group of radioiodine refractory (RAI-R) patients. This strategy may exploit CXCR4 receptors as potential targets for treatment with alpha/beta radionuclide theranostic in this sub-set of thyroid cancer patients. Materials and Methods: A total of 10 (3-Male: 7-Female, mean age = 48.8 ± 12.9 years) thyroid cancer patients documented as refractory to radioiodine treatment were recruited in the study. All the patients underwent both 18F-FDG and 68Ga-Pentixafor PET/CT within a gap of 7- days. Whole body acquisitions from skull to mid-thigh (7-9 bed positions) were done at 1 hour post injection with mean injected dose of 7.52 0.71 mCi & 2.26 0.55 mCi of 18F-FDG & 68Ga-Pentixafor respectively. The reconstructed images projected in three planes (cross-sectional; coronal and sagittal) were used for visual and quantitative analysis for both the scans. A head-to-head lesion-based comparison was done for the PET procedures. Results: All the ten patients showed scan evidence of residual/metastatic disease on 18F-FDG while 9/10 showed 68Ga-Pentixafor scan positivity. Further, 2/10 patients with remnant/residual disease in thyroid bed showed concurrent finding of increased tracer uptake on both 18F-FDG & 68Ga-Pentixafor scan. 18F-FDG scan showed increased tracer uptake in locoregional lymph nodes in all the ten patients whereas increased tracer uptake was seen in 9/10 of these patients on 68Ga-Pentixafor scan. Three patients had metastatic lung disease with increased 18F-FDG uptake out of which two patients had showed increased CXCR4 expression on 68Ga-Pentixafor scan. One patient with skeletal metastatic had concurrent finding of increased tracer uptake in dorsal vertebra on both the PET procedures. Upon lesion based analysis a total of 55 lesions showed increased tracer uptake on 18F-FDG and 37 of these lesions showed increased CXCR4 expression on 68Ga-Pentixafor scan. The mean SUVmax on 68Ga-Pentixafor as compared to 18F-FDG PET (3.2 ± 3.1 vs. 10.2 ± 8.2) was significantly lower. Conclusion: This preliminary study documents the significant CXCR4 receptors’ expression in 9/10 (90.0%) of the RAI-R patients. Whereas, in the lesion wise analysis, only 37/55 (67.0%) of the FDG avid lesions showed CXCR4 receptors expression on 68Ga-pentixafor PET/CT imaging. This may open an opportunity to treat a significant proportion of RAI-R patients with upcoming CXCR4 targeting alpha and beta emitters. The results of this pilot study however, needs validation in a large cohort of patients and correlation with detailed IHC analysis.
