Personalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and therapeutic applications. This international multi-center study aims to investigate the clinical measurement accuracy of radionuclide calibrators for 7 radionuclides used in theragnostics: 99mTc, 111In, 123I, 124I, 131I, 177Lu, and 90Y. In total, 32 radionuclide calibrators from 8 hospitals located in the Netherlands, Belgium, and Germany were tested. For each radionuclide, a set of four samples comprising two clinical containers (10-mL glass vial and 3-mL syringe) with two filling volumes were measured. The reference value of each sample was determined by two certified radioactivity calibration centers (SCK CEN and JRC) using two secondary standard ionization chambers. The deviation in measured activity with respect to the reference value was determined for each radionuclide and each measurement geometry. In addition, the combined systematic deviation of activity measurements in a theragnostic setting was evaluated for 5 clinically relevant theragnostic pairs: 131I/123I, 131I/124I, 177Lu/111In, 90Y/99mTc, and 90Y/111In. For 99mTc, 131I, and 177Lu, a small minority of measurements were not within ± 5% range from the reference activity (percentage of measurements not within range: 99mTc, 6%; 131I, 14%; 177Lu, 24%) and almost none were outside ± 10% range. However, for 111In, 123I, 124I, and 90Y, more than half of all measurements were not accurate within ± 5% range (111In, 51%; 123I, 83%; 124I, 63%; 90Y, 61%) and not all were within ± 10% margin (111In, 22%; 123I, 35%; 124I, 15%; 90Y, 25%). A large variability in measurement accuracy was observed between radionuclide calibrator systems, type of sample container (vial vs syringe), and source-geometry calibration/correction settings used. Consequently, we observed large combined deviations (percentage deviation > ± 10%) for the investigated theragnostic pairs, in particular for 90Y/111In, 131I/123I, and 90Y/99mTc. Our study shows that substantial over- or underestimation of therapeutic patient doses is likely to occur in a theragnostic setting due to errors in the assessment of radioactivity with radionuclide calibrators. These findings underline the importance of thorough validation of radionuclide calibrator systems for each clinically relevant radionuclide and sample geometry.

中文翻译：

---

国际上对核医学检验学中放射性核素校准物准确性的多中心研究

基于Theragnostics的个性化分子放射疗法需要准确定量诊断和治疗应用中给予患者的放射药物活性。这项国际性的多中心研究旨在研究用于矫正术中的7种放射性核素的放射性核素校准剂的临床测量准确性：99mTc，111In，123I，124I，131I，177Lu和90Y。总共对位于荷兰，比利时和德国的8家医院的32个放射性核素校准物进行了测试。对于每种放射性核素，测量了一组四个样品，包括两个带有两个填充量的临床容器（10毫升玻璃小瓶和3毫升注射器）。每个样品的参考值由两个认证的放射性校准中心（SCK CEN和JRC）使用两个二级标准电离室确定。对于每种放射性核素和每种测量几何形状，确定了所测得活性相对于参考值的偏差。此外，针对5种临床相关的鼻窦炎对评估了鼻窦炎活动度的组合系统偏差：131I / 123I，131I / 124I，177Lu / 111In，90Y / 99mTc和90Y / 111In。对于99mTc，131I和177Lu，一小部分测量值不在参考活动的±5％范围内（测量百分比不在此范围内：99mTc，6％； 131I，14％； 177Lu，24％），几乎没有不在±10％范围内。但是，对于111In，123I，124I和90Y，超过一半的测量值在±5％范围内不准确（111In，51％; 123I，83％; 124I，63％; 90Y，61％），并非都在±10％的范围内（111In，22％; 123I，35％； 124I，15％； 90Y，25％）。在放射性核素校准器系统，样品容器的类型（样品瓶与注射器）和所用源几何校准/校正设置之间，观察到测量精度存在较大差异。因此，我们观察到了被研究的鼻咽管对的较大的组合偏差（百分比偏差>±10％），尤其是对于90Y / 111In，131I / 123I和90Y / 99mTc。我们的研究表明，由于使用放射性核素校准剂评估放射性存在错误，因此在鼻咽科治疗中可能会发生患者治疗剂量的严重高估或低估的情况。