Successful Identification of Coexisting Renal Carcinoid and Giant Cell Arteritis with [⁶⁸Ga]Ga-DOATATOC Positron Imaging

INTRODUCTION

Giant cell arteritis (GCA) is a chronic granulomatous vasculopathy typically characterised by temporal headache, jaw claudication, visual disturbance, and temporal artery thickening.^[1] Although temporal artery biopsy is highly specific, many patients present atypically with systemic inflammatory features, including polymyalgia-like symptoms or thoracic aortic aneurysm.^[2] Thus, no single symptom or sign is pathognomonic. Whole-body molecular imaging, particularly [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography/computed tomography (PET/CT), provides accurate pan-arterial disease mapping prior to treatment initiation, a role officially recognised in the 2022 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria for large-vessel vasculitis.^[3]

GCA may coexist with chronic diseases, further complicating diagnosis owing to overlapping clinical features. Several reports describe new-onset GCA occurring alongside malignancy, whether at initial presentation, at recurrence, or during the progression of cancer.^[4,5] In such scenarios, molecular imaging offers a compelling tool to assess both the tumour burden and the inflammatory extent within a single examination.

Recent advances in oncologic imaging have highlighted somatostatin receptor (SSTR) agonist PET/CT as a sensitive modality for detecting neuroendocrine tumours (NETs),particularly gastroenteropancreatic NETs.^[6] Beyond diagnosis, this approach has been incorporated into theragnostic strategies.^[7]Reports of its use in non-gastroenteropancreatic NETs, such as renal NETs, remain scarce.^[8] Although highly specific for NETs, [⁶⁸Ga]Ga-DOTA-Tyr3-octreotide ([⁶⁸Ga]Ga- DOTATOC) PET/CT can also demonstrate uptake under nononcologic conditions, broadening its potential applications.^[9] The present case describes a unique and previously unreported occurrence of concurrent new-onset GCA and recurrent renal NET and explores the possible underlying mechanisms as well as the clinical utility of this novel imaging technique.

CASE REPORT

A 69-year-old female patient presented with a history of T1N0M0 stage I renal carcinoid diagnosed eight years ago, which was treated with a right radical nephrectomy, leading to a documented remission. Over the past six weeks, the patient experienced progressive headaches, jaw claudication, neck pain, and bone pain, which raised clinical suspicion for disease recurrence and warranted further diagnostic evaluation. Initial laboratory findings showed mild hepatic transaminitis with an aspartate transaminase of 56 IU/L and an alanine transaminase of 64 IU/L; all other hematologic, renal, and hepatic parameters were within normal limits.

[⁶⁸Ga]Ga-DOTATOC PET/CT scan [Supplementary Table 1] was performed to evaluate for disease recurrence. Maximum intensity projection images revealed multiple [⁶⁸Ga]GaDOTATOC-avid foci [Fig 1A, arrows] and diffuse cardiac [⁶⁸Ga]Ga-DOTATOC expression [Fig 1A, spade]. A diffuse heterogeneous [⁶⁸Ga]Ga-DOTATOC uptake was noted tracking the course of the aorta and its main branches [Fig 1A, asterisks]. Fused PET/CT images identified an SSTR-avid intrahepatic mass with a necrotic centre, consistent with locoregional recurrence [Fig 1B, C; arrows]. Additionally, multiple SSTR- avid hepatic [Fig 1B-D, arrowheads] and skeletal lesions [Fig 1E, F; curved arrows] were observed. Heterogeneous [⁶⁸Ga]Ga-DOTATOC uptake was observed throughout the cardiac region [Fig 1A, G; spades], with a notable retrocardiac [⁶⁸Ga]Ga-DOTATOC-avid aneurysmal dilation of the descending thoracic aorta [Fig 1G, dotted arrow]. This was accompanied by increased heterogeneous [⁶⁸Ga]Ga-DOTATOC expression affecting the remainder of the aorta, bilateral iliofemoral branches, both subclavian arteries, and both internal carotid arteries [Fig 1A, H; asterisks], with a maximum standardised uptake value (SUVmax) of 8.1 [Fig 2A-C; dotted arrows]. The overall clinical and imaging picture was consistent with multisite disease recurrence, while the vascular [⁶⁸Ga]Ga- DOTATOC expression raised suspicion for coexisting large vessel vasculitis. Further biochemical correlation with an erythrocyte sedimentation rate (ESR) was requested, which was elevated at 87 mm/hr. Clinical diagnosis of GCA was affirmed with total sum GCA score of 9 as per 2022 ACR/EULAR Classification Criteria [Fig 2D, E]. The patient is scheduled to undergo management with Lanreotide and high-dose corticosteroids for adequate control of both pathologies. Lanreotide was selected as monotherapy for renal NET to minimise potential nephrotoxic burden given the presence of a single functioning kidney.

Close

Fig 1: (A) Maximum intensity projection image reveals multiple [⁶⁸Ga]Ga-DOTATOC foci (arrows), diffuse myocardial uptake (spade), and heterogeneous [⁶⁸Ga]Ga-DOTATOC expression along the aorta and branches (asterisks); (B-D) Positron emission tomography/computed tomography (PET/CT) shows an infrahepatic mass with necrosis (arrows in B and C), several hepatic lesions (arrowheads in B -D), diffuse myocardial uptake (spade in B), and heterogeneous [⁶⁸Ga]Ga-DOTATOC expression along the aorta (asterisk in B); (E and F) Axial PET/CT shows multiple skeletal lesions (curved arrows); (G) Axial PET/CT notes heterogeneous cardiac uptake (spade) and aneurysmal dilation near the descending thoracic aorta (dotted arrow); (H) Coronal PET/CT displays heterogeneous [⁶⁸Ga]Ga-DOTATOC uptake across the aorta and major branches (asterisks). PET/CT: Positron emission tomography/computed tomography

Export to PPT

Close

Fig 2: (A-C) Axial computed tomography (CT), positron emission tomography (PET), and PET/CT images demonstrating heterogeneous peripheral [⁶⁸Ga]Ga DOTATOC uptake confined to the abdominal aortic arterial walls (dotted arrows); (D) Graphical representation illustrates the panarterial and aneurysmal involvement pattern in giant cell arteritis (GCA), closely resembling the findings in our presented case; (E) Overview of the clinical and biochemical criteria in our patient yielded a cumulative score of 9, supporting the clinical confirmation of GCA. ESR: Erythrocyte sedimentation rate.

Export to PPT

DISCUSSION

The present case illustrates an uncommon coexistence of recurrent renal NET with clinically confirmed GCA, creating complex challenges in imaging interpretation using somatostatin receptor– targeted modalities. [⁶⁸Ga] Ga-DOTATOC PET/CT study proved crucial in accurately identifying both locoregional recurrence and metastatic spread, revealing intense tracer avidity. The study was also vital in providing effective management guidance through the successful identification of the renal NET burden, thereby affirming disease recurrence and opting for further biochemical surveillance to establish the clinical diagnosis of GCA.

Literature addressing the diagnostic relevance of [⁶⁸Ga]Ga-DOTATOC PET/CT specifically for renal NET evaluation remains limited largely due to the rarity of primary renal NET pathologies.^[8] Owing to similar SSTR upregulation, the performance characteristics of DOTA-based PET/ CT in renal NET show no difference to those reported for gastroenteropancreatic NET.^[8] A previous meta-analysis revealed that [⁶⁸Ga]Ga-DOTATOC has a pooled sensitivity and specificity of 92% and 82%, respectively, in the detection of NET pathologies.^[10]

While its sensitivity is well recognised, one of the more challenging aspects of interpreting [⁶⁸Ga]Ga- DOTATOC imaging lies in its non-specificity.^[9] Beyond NET pathologies, increased avidity is also reported in granulomatous diseases such as sarcoidosis and tuberculosis.^[9] This phenomenon reflects SSTR2 overexpression on activated inflammatory cells, particularly macrophages. ^[9,11] This expression provides a biological explanation for the false-positive findings but simultaneously opens promising avenues for extending somatostatin receptor–targeted imaging to inflammatory and autoimmune disorders, highlighting its evolving role beyond conventional oncologic applications.^[9,11]

Evidence regarding SSTR PET imaging in large vessel vasculitis remains limited but promising. Ćorović et al. demonstrated that [⁶⁸Ga]Ga-DOTA-Tyr3-octreotate ([⁶⁸Ga] Ga-DOTATATE) PET provides detection sensitivity comparable to [¹⁸F]FDG PET, while achieving superior lesion-to- background ratios in vascular and myocardial regions.^[12] Moreover, treatment response was reflected by declining SSTR2 uptake, highlighting its potential for both disease assessment and therapeutic monitoring.^[12]

In this case, the identification of diffuse myocardial and panarterial uptake on [⁶⁸Ga]Ga-DOTATOC PET/CT, accompanied by a thoracic aortic aneurysm, suggested an ongoing inflammatory vasculopathy unrelated to the original oncologic indication. Aortic aneurysmal dilatation is a well-recognised manifestation of GCA, affecting up to one-fifth of patients, predominantly involving the thoracic segment, and often remaining clinically silent until complications occur.^[13]Accurate interpretation, therefore, necessitates correlation with patient history and appropriate laboratory evaluation to support GCA diagnosis.

Few reports have documented GCA in cancer patients, with its pathophysiological link yet to be fully understood. Proposed mechanisms include paraneoplastic immune dysregulation.^[4,14,15] While [¹⁸F]FDG PET/CT has been predominantly used for diagnosis and monitoring,^[15-17] the application of [⁶⁸Ga]Ga-DOTATOC PET/CT introduces a novel approach capable of concurrently assessing oncologic and vascular inflammatory processes. To date, the utility of SSTR PET imaging in the treatment monitoring of vasculitis is not documented. Therefore, near future studies should systematically evaluate the potential role of SSTR PET imaging in assessing disease activity, guiding therapy, and monitoring treatment response in patients with vasculitis.

CONCLUSION

This case highlights the expanding role of [⁶⁸Ga] Ga-DOTATOC PET/CT as an SSTR imaging agent beyond neuroendocrine oncology. This finding illustrates how SSTR-targeted imaging may contribute not only to accurate tumour characterisation but also to the evaluation of large vessel vasculitis, bridging the domains of oncology and immunology within a single imaging platform.