BackgroundPersonalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and... Show moreBackgroundPersonalized 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: Tc-99m, In-111, I-123, I-124, I-131, Lu-177, and Y-90.MethodsIn 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: I-131/I-123, I-131/I-124, Lu-177/In-111, Y-90/Tc-99m, and Y-90/In-111.ResultsFor Tc-99m, I-131, and Lu-177, a small minority of measurements were not within 5% range from the reference activity (percentage of measurements not within range: Tc-99m, 6%; I-131, 14%; Lu-177, 24%) and almost none were outside +/- 10% range. However, for In-111, I-123, I-124, and Y-90, more than half of all measurements were not accurate within +/- 5% range (In-111, 51%; I-123, 83%; I-124, 63%; Y-90, 61%) and not all were within +/- 10% margin (In-111, 22%; I-123, 35%; I-124, 15%; Y-90, 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 Y-90/In-111, I-131/I-123, and Y-90/Tc-99m.Conclusions 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. Show less
Brown adipose tissue (BAT) is present in human adults and the current gold standard to visualize and quantify BAT is [F-18] FDG PET-CT. However, this method fails to detect BAT under insulin... Show moreBrown adipose tissue (BAT) is present in human adults and the current gold standard to visualize and quantify BAT is [F-18] FDG PET-CT. However, this method fails to detect BAT under insulin-resistant conditions associated with ageing and weight gain, such as type 2 diabetes. The aim of this study was to develop a novel triglyceride-based tracer for BAT. For this purpose we designed a dual-modal fluorescent/PET fatty acid tracer based on commercially available BODIPY-FL-C-16, which can be esterified to its correspondent triglyceride, radiolabeled and incorporated into pre-synthesized chylomicron-like particles. BODIPY-FL-C-16 was coupled to 1,2-diolein with a subsequent radiolabeling step resulting in [F-18] BODIPY-C-16-triglyceride that was incorporated into chylomicron-like particles. Various quality control steps using fluorescent and radioactive methods were conducted before BAT visualization was tested in mice. Triglyceride synthesis, radiolabeling and subsequent incorporation into chylomicron-like particles was carried out in decent yields. This radiotracer appeared able to visualize BAT in vivo, and the uptake of the radiotracer was stimulated by cold exposure. The here reported method can be used to incorporate radiolabeled triglycerides into pre-synthesized chylomicron-like particles. Our approach is feasible to visualize and quantify the uptake of triglyceride-derived fatty acids by BAT. Show less
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