Translate this page into:
Assessment of the Performance of the Dose Calibrator Used in Radioactivity Measurement
Address for correspondence: Mr. Dinh Xuan Hoang, 01 Nguyen Tu Luc Street, Ward 8, Da Lat City, Lam Dong Province, Vietnam. E mail: hoangdx@dnri.vn
-
Received: ,
Accepted: ,
This article was originally published by Wolters Kluwer - Medknow and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Aims:
This study aimed to evaluate the principal technical characteristics of a well-type gas-filled ionization chamber dose calibrator used in measuring radiopharmaceutical activity, namely accuracy, repeatability, and linearity. Furthermore, this work also explored the correlation between the device’s response and the position and volume of the radiopharmaceutical I-131.
Materials and Methods:
Experimental measurements were conducted on the ATOMLAB 500 dose calibrator using NIST traceable Cs-137 source to determine the accuracy and repeatability. For the linearity test, the Tc-99m solution produced at the Dalat Nuclear Research Institute, Vietnam was utilized to examine the performance of the device over a wide measurement range. Effects resulting from different volumes and measuring positions were also determined by experiments and Monte Carlo simulations.
Results:
Based on acceptance test results, it is revealed that the dose calibrator’s characteristics comply with international standards, where the deviations of accuracy, repeatability, and linearity are all lower than 1.0%. The response of the dose calibrator to different measuring positions and volumes was well controlled. To rectify the discrepancy in the response to the changes in solution volume, correction functions were proposed.
Conclusions:
It is concluded that the dose calibrator is suitable for radioactivity quantification and adheres to standards recommended by international organizations for nuclear medicine activities. The outcome of this work will serve as the foundation for establishing a standard for I-131 radiopharmaceuticals’ radioactivity in Vietnam.
Keywords
Dose calibrator
measurement accuracy
Monte Carlo simulation
nuclear medicine
radiopharmaceutical
Introduction
In nuclear medicine, the accuracy and reliability of radiopharmaceutical activity are prerequisite factors, among others, to ensure the quality and effectiveness of diagnosis and treatment processes.[1] Depending on regulations and actual situations, requirements for the accuracy of the “true dose” may vary from country to country. Nevertheless, the deviation in radiopharmaceutical activity at the end-user level should not exceed 5%–10%, as recommended by the International Atomic Energy Agency and the American National Standards Institute.[23]
Typically, radiopharmaceutical activity is assayed using a dose calibrator (or radionuclide calibrator), which is a device equipped with a pressurized ionization chamber connected to an electrometer. This setup converts the ionization current produced in the chamber’s active volume into radioactivity. Due to its advantages of reasonable cost, quick response, and ease of operation and calibration, the dose calibrator is widely utilized in nuclear medicine facilities, including manufacturer’s laboratories, hospitals, and clinics.
When using the dose calibrator for radiopharmaceutical quantification, the user must thoroughly understand the device’s performance and the factors that influence the accuracy of the measured activity. Essentially, the three main specifications that must be considered at first glance are accuracy, repeatability, and linearity. These features must be carefully examined before putting the device into operation.[45] The tests for these characteristics also help the user determine the uncertainty of repeatability and linearity that will be included in the uncertainty budget for activity measurements using the device.
Moreover, the deviation in the response of the dose calibrator arises due to differences in geometric factors, such as source volume and measuring position, which might significantly influence the accuracy of activity measurements.[678] As a result, it is important to consider these variables to ensure accurate and reliable results when using the device to measure radiopharmaceuticals.
The goal of this study is to experimentally verify the characteristics of the dose calibrator through acceptance tests. This study also explores how the device’s response depends on the displacement of the measuring position and the change in source volume for the case of the I-131 radioactive solution produced at the Dalat Nuclear Research Institute (DNRI). Based on the outcomes obtained, adjustments might be suggested to improve the accuracy and reliability of measurement results. The results of the study could be valuable in developing suitable measurement protocols to comply with the quality assurance (QA) standards for radiopharmaceuticals at the DNRI.
Materials and Methods
Dose calibrator
The dose calibrator used in this study is the ATOMLAB 500, manufactured by Biodex Medical Systems, Inc., US. It features a well-type ionization chamber with argon gas and a high-impedance electrometer for current measurement. A connected tablet allows users to manage measurement data. The dose calibrator can measure 97 isotopes with activities from 0.01 μCi to tens of Ci for photon energies from 25 keV to 3000 keV. Primary technical specifications of the ATOMLAB 500 dose calibrator can be found in Table 1.[9]
| Specifications | Value |
|---|---|
| Activity range | 0.01 µCi –100 Ci of Tc-99 m |
| Energy range | 25 keV –3 MeV photons |
| Electrometer linearity | ±1% or 0.2 (µCi), whichever is greater |
| Electrometer accuracy | ±1% or 0.2 (µCi), whichever is greater |
| Repeatability | ±0.3% above 1 (mCi) |
Radiation measurement mechanism of the ATOMLAB 500 dose calibrator
The principle for detecting and measuring the activity of radio-isotopes is based on the ionization current generated when photon radiation enters and interacts with the gas of the dose calibrator’s chamber. This current is expressed by:
Where I is the ionization current (in A), Ēdeposited is the average energy deposited in the chamber per disintegration (in eV), A is the activity of the source (in Bq), e is the electronic charge (in C), and W is the average energy in eV expended for the creation of an ion pair in the chamber (W = 26.4 eV for Argon).
The response of the ATOMLAB 500 to a photon of energy E is defined as:
For multiphoton emission isotopes, the total response is calculated by:
where RE is the photon energy, and PE is the photon emission probability.
The response of the dose calibrator for a specific isotope is used to calculate the calibration factor (CF) of that isotope. For the ATOMLAB 500, the CF of Co-60 is defined to be equal to 5.0. The CF for any isotope is determined by:
In modern laboratories, CFs are determined experimentally by measuring the current generated in the chamber using standard sources. Alternatively, Monte Carlo simulations can be used to calculate CFs, especially in laboratories with limited infrastructure.
Acceptance tests
In this study, the ATOMLAB 500 dose calibrator underwent acceptance tests to verify its accuracy, repeatability, and linearity. The accuracy test is conducted to determine the error of the dose calibrator’s reading when measuring a standard source. In this case, 10 measurements were taken on the dose calibrator using a NIST-traceable Cs-137 source with an activity of 208.8 μCi during the experiment. For each measurement, 10 values were collected, and the average of these values was used to calculate the error by:
where ĀMeasured represents the average activity of 10 measured values on the dose calibrator, and AStandard represents the activity of the standard source.
Regarding repeatability, a total of 50 measurements were executed, and their standard deviation (Std.) and average activity were recorded. Subsequently, the relative Std. (RSD) was computed for each measurement as a percentage using Equation (6), followed by the calculation of the pooled RSD using Equation (7).
where vi represents the degree of freedom and is defined as (n - 1), and n is the number of independent observations of the measurement. In this test, there are 10 independent values collected for each measurement, so vi equals 9.
The purpose of the linearity test is to determine whether the device performs effectively in a wide range of activities, typically ranging from 100 μCi to several hundred mCi. To perform the test, a vial containing 10 mL of Tc-99m solution with an initial activity of 870 mCi was utilized. The experiment started by measuring the activity of Tc-99m and recording the initial value (A0) at time t0. Subsequent measurements were taken and recorded at 3-h intervals until the activity decays to below 100 μCi. The measured values at time t, denoted as AMeas.(t), were then compared with the calculated activity, denoted by ACalc. (t), which is determined from A0 using the decay equation. The linearity error is determined using the following formula:
The data analysis for this study was accomplished utilizing MATLAB, while the graphical representations were created using both MATLAB and Microsoft Excel.
Effects of source volume and position
To investigate the influence of volume on activity, the test was started by measuring a 10R borosilicate glass vial [Figure 1] containing 1 mL I-131-NaI solution with an activity concentration of 5 mCi/mL. Subsequently, add 1 mL of distilled water to the vial and record the activity value. Repeat this process until the solution in the vial reaches 10 mL. The activity measured at V = 5 mL will be considered the reference value for comparisons with the values at other volumes.
Concerning position dependence, the source containing 5 mL solution whose activity of 5 mCi was utilized. The recorded activity results encompass measurements at the center of the dipper and points to the left and right of the center, with increments of 1 mm.
Monte Carlo simulations
To simulate the response of the dose calibrator for various volumes and positions, MC simulations were performed using the MCNP5 computer code. Simulations were carried out by adjusting the volume and position of the source, following the experimental procedure outlined in Section 2.4. The deposited energy for different configurations was calculated and assumed to be proportional to the activity of the source. The response of the vial with a volume of 5 mL positioned at the center of the dipper was adopted as the reference value.
Regarding the simulation and calculation of the response-energy curve, the problem entails finding the average energy deposited in the chamber for each single-energy photon reaching the detector. This was achieved by simulating interactions and energy deposition for photon energies from 25 keV to 3000 keV. Equations (1-4) were applied to determine the energy-response curve and new CFs for isotopes of interest.
Figure 2 illustrates the dose calibrator configuration and the corresponding MCNP5 model employed for MC simulations in this study.
Results
Acceptance test results
The results of 10 separate accuracy tests on the dose calibrator showed errors ranging from −1.77% to −2.20%, with an average error of −1.96%. Detailed results can be found in Table 2. It is noteworthy that these tests were conducted using the manufacturer-established CFCs-137 of 17.1.
| Test number | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
| ĀMeasusred (µCi) | 204.7 | 204.9 | 205 | 204.8 | 204.3 | 204.2 | 204.8 | 205.1 | 204.4 | 204.9 |
| AStandard (µCi) | 208.8 | 208.8 | 208.8 | 208.8 | 208.8 | 208.8 | 208.8 | 208.8 | 208.8 | 208.8 |
| Error (%) | −1.96 | −1.87 | −1.82 | −1.92 | −2.16 | −2.20 | −1.92 | −1.77 | −2.11 | −1.87 |
The dose calibrator’s repeatability and linearity results are shown in Figures 3 and 4, respectively. The repeatability error ranged from 0.22% to 0.54%, with an RSDpooled of 0.38%. As shown in Figure 4, the upper graph shows the measured and calculated activity of Tc-99 m at different time points, whereas the lower graph displays the linearity error. The maximum linearity error of 0.56% occurred at t = 54 h with an activity of approximately 1.8 mCi.
Response-energy curve
Due to the significant error in the accuracy test, as given in Table 2, a new response-energy curve was reconstructed using MC simulations and illustrated in Figure 5. In the figure, the vertical axis represents photon energies (in MeV), whereas the horizontal axis corresponds to the ionization current (in nA) generated in the chamber for every 3.7 × 107 (or 1 mCi) photon of a certain energy emitted from the source. In addition, the photon energies of Co-60 and their corresponding responses were indicated in the figure. The total response for Co-60 was calculated to be 1.35 × 10−1 (nA/mCi) using Equation (3). Similarly, the total response for Cs-137 was determined to be 3.82 × 10E−2 (nA/mCi). The data for photon energies and emission probabilities of these isotopes were obtained from NUDAT3 (available at: https://www.nndc.bnl.gov/nudat3/indx_dec.jsp). Eventually, the new CF for Cs-137 was calculated to be 17.6 using Equation (4).
To validate the calculation results, we adjusted the CF of Cs-137 from 17.1 to 17.6. After remeasuring the Cs-137 standard source, the accuracy error was significantly reduced to an average value of 0.21% [Figure 6].
Geometric effect
Figures 7 and 8 illustrate how the activity measurement results vary with different measurement positions and volumes, respectively. In these figures, the response of 1.0 corresponds to the “reference geometry,” i.e., the response for a 10R glass vial containing 5 mL of I-131 solution positioned at the bottom center of the dipper. In Figure 7, negative numbers on the X-axis correspond to the measurement positions on the left of the dipper’s center, and vice versa. The maximum deviation due to the displacement of the source was observed to be approximately 0.2%. As for the volume dependence, the response exhibited a decrease with increasing volume. Specifically, the responses at V = 1 mL and V = 10 mL were 1.007 and 0.998, respectively, relative to the response at V = 5 mL.
Discussion
The accuracy test results, as shown in Table 2, revealed that the dose calibrator underestimated the activity of the Cs-137 standard source. According to the calibration certificate when the device was manufactured, the argon mass was 7.169 g, and the accuracy error when measuring Cs-137 with CF = 17.1 was −0.51%. However, during the experiment, the mass of argon was recorded to be 6.98 g. We supposed that the loss in argon mass resulted in the reduction of ionization events inside the active volume of the dose calibrator, and the activity decreased accordingly. Further studies are needed to determine the impact of argon gas amount on activity measurement results accuracy.
The measured data for acceptance tests, as visually represented in Figures 3 and 4, demonstrated the outstanding repeatability and linearity of the ATOMLAB 500 dose calibrator. Based on experiment data, the pooled RSD for repeatability was computed to be 0.38%. Regarding linearity, the maximum relative deviation between the measured and calculated values is 0.56%. These results underscore the device’s high reliability and its ability to provide accurate results across a wide range of measurements.
Even though the accuracy error is still within the permissible limit (±5%), it is crucial to reduce the error because higher accuracy leads to more effective medical treatment. In addition, other factors can contribute to the total measurement error, such as sample impurities and stability. The calculation of the new CF for Cs-137 based on MC simulations has revealed a significant improvement in accuracy, where the error was reduced to −0.21%. The improvement in the accuracy confirms the reliability of simulation results, supporting the application of this curve in calculations for other photon-emitting isotopes.
The results for the position dependence, as shown in Figure 7, indicate that the activity measurements are not significantly affected by the sample position. This problem could be addressed by implementing suitable sample measurement procedures to ensure that the sample remains consistently positioned at the center of the dipper.
In order to account for the deviations observed in the dose calibrator's response when different solution volumes are used, as shown in Figure 8, we developed two fitting functions based on experimental data for two specific volume ranges: 1–5 mL and 5–10 mL [Figure 9]. Using these functions significantly improves the accuracy of activity measurements for volumes other than 5 mL.
Conclusions
Through meticulous experimental measurements, this study comprehensively investigated the technical characteristics of the ATOMLAB 500 dose calibrator. The results obtained for repeatability and linearity play a vital role in determining uncertainties in radiopharmaceutical activity measurements. The use of CF derived from the new responseenergy curve resulted in a significant improvement in measurement accuracy, indicating the effective application of MC simulation for calibrating well-type ionization chamber dose calibrators.
The response of the device was observed to exhibit slight dependencies on both source geometry and position, as evidenced by simulation and experimental results across different measuring geometries. This finding highlights the need to develop appropriate measurement procedures and QA programs to improve the reliability of radiopharmaceutical activity.
The outcomes of this work are expected to be serviceable for those employing dose calibrators in routine activity measurement, such as radiopharmaceutical production labs or nuclear medicine clinics. These findings will enable them to adapt, upgrade, or refine measurement procedures to achieve heightened precision in their measurements.
Conflicts of interest
There are no conflicts of interest.
This study was supported by the Ministry of Science and Technology of Vietnam under the project code No. 04/HĐ/ĐTCB for the fiscal year 2022-2023.
References
- Nuclear medicine physics : a handbook for teachers and students. International Atomic Energy Agency 2014
- [Google Scholar]
- Quality Assurance for Radioactivity Measurements in Nuclear Medicine. In: Technical Report Series No. 454. Vienna, Austria: International Atomic Energy Agency (IAEA); 2006.
- [Google Scholar]
- Calibration and Usage of “Dose Calibrator” Ionization Chambers for the Assay of Radionuclides. In: (Reaffirmation of ANSI N42.13-1986). Washington, DC: American National Standards Institute; 2004.
- [Google Scholar]
- The Selection, Use, Calibration, and Quality Assurance of Radionuclide Calibrators Used in Nuclear Medicine. 2012
- [Google Scholar]
- Measurement Good Practice Guide No. 93. Protocol for Establishing and Maintaining the Calibration of Medical Radionuclide Calibrators and their Quality Controls. United Kingdom: NPL; 2006.
- [Google Scholar]
- Discrepancies in dose calibrator assays for various forms of therapeutic iodine-131. J Nucl Med Technol. 1984;12:84-6.
- [Google Scholar]
- Syringe shape and positioning relative to efficiency volume inside dose calibrators and its role in nuclear medicine quality assurance programs. Appl Radiat Isot. 2009;67:1104-9.
- [Google Scholar]
- Assessment of the relative contribution of volume and concentration changes in yttrium-90 labelled resin microspheres on ionization chamber measurements. Australas Phys Eng Sci Med. 2017;40:943-8.
- [Google Scholar]
- Biodex Medical Systems, Inc., Atomlab 500TM dose calibrator, Instructions for use. 2020
- [Google Scholar]