Radiation dosimetry of the translocator protein ligands [18F]PBR111 and [18F]PBR102.

INTRODUCTION: The translocator protein (TSPO) ligands [18F]PBR111 and [18F]PBR102 show promise for imaging neuroinflammation. Our aim was to estimate the radiation dose to humans from primate positron emission tomography (PET) studies using these ligands and compare the results with those obtained from studies in rodents. METHODS: [18F]PBR111 and [18F]PBR102 PET-computed tomography studies were carried out in baboons. The cumulated activity in the selected source organs was obtained from the volume of interest time-activity curves drawn on coronal PET slices and adjusted for organ mass relative to humans. Radiation dose estimates were calculated in OLINDA/EXM Version 1.1 from baboon studies and compared with those calculated from Sprague-Dawley rat tissue concentration studies, also adjusted for relative organ mass. RESULTS: In baboons, both ligands cleared rapidly from brain, lung, kidney and spleen and more slowly from liver and heart. For [18F]PBR111, the renal excretion fraction was 6.5% and 17% for hepatobiliary excretion; for [18F]PBR102, the renal excretion was 3.0% and 15% for hepatobiliary excretion. The estimated effective dose in humans from baboon data was 0.021 mSv/MBq for each ligand, whilst from rat data, the estimates were 0.029 for [18F]PBR111 and 0.041 mSv/MBq for [18F]PBR102. CONCLUSION: Biodistribution in a nonhuman primate model is better suited than the rat model for the calculation of dosimetry parameters when translating these ligands from preclinical to human clinical studies. Effective dose calculated from rat data was overestimated compared to nonhuman primate data. The effective dose coefficient for both these TSPO ligands determined from PET studies in baboons is similar to that for [18F]FDG.

The clinical effects of thyroid stunning after diagnostic whole-body scanning with 185 MBq 131I.

"Thyroid stunning" from diagnostic iodine-131 imaging prior to ablative therapy with (131)I for well-differentiated thyroid carcinoma has been well reported, but documentation of the effect on clinical outcome is sparse. The purpose of this retrospective study was to investigate the clinical effects of stunning. The outcome of (131)I ablative therapy in a group of patients ( n=36) who had diagnostic scans using 185 MBq (5 mCi) of (131)I was compared with that in a group ( n=36) who had diagnostic scans using 740 MBq (20 mCi) of (123)I. Patients were imaged at least 4 weeks after near-total thyroidectomy, prior to their first (131)I ablative therapy. Follow-up imaging was performed every 3-6 months, and further (131)I treatment administered when indicated. A group of patients ( n=36) who proceeded directly to their first therapy dose without a diagnostic scan and were followed up with (123)I was compared with the group who did have a (123)I diagnostic scan prior to the first ablative therapy. The efficacy of therapy was evaluated using ablation of the thyroid, evidenced by absence of uptake in the thyroid bed on the diagnostic scan, as the endpoint. Only 47% of patients in the (131)I diagnostic group had the thyroid gland ablated after a single administration of (131)I therapy, compared with 86% in the (123)I diagnostic group ( P<0.005). Patients who had (131)I diagnostic scans required higher total (131)I therapeutic activity (6.7 GBq or 180 mCi) to ablate the thyroid gland than those in the (123)I diagnostic group (4.4 GBq or 119 mCi). There was no difference in outcome between the group who did and the group who did not have a diagnostic study with (123)I prior to their first ablative therapy. The difference in outcome between the (131)I and the (123)I diagnostic groups demonstrates that the efficacy of (131)I therapy is reduced subsequent to the use of 185 MBq of (131)I for diagnostic imaging. This indicates that the phenomenon of stunning is clinically significant and affects the outcome of therapy.