Abstract
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Objectives: The goal of this study was to study the biodistribution, metabolism and radiation dosimetry of the first human control studies using 18F-Tetrafluoroborate (18F-TFB). Achieving this will allow us to understand if 18F-TFB is a safe radiopharmaceutical for imaging human sodium iodide symporter (NIS) expressing cells.
Methods: Eight healthy volunteers (4-M/ 4-F) were enrolled in the study from 9/20/16 to 12/13/16. 18F-TFB was synthesized with a decay-corrected radiochemical yield of 32 ± 2% and >98% radiochemical purity. Specific radioactivity of 2.2 ± 0.9 GBq/µmol was achieved from starting 18F-fluoride radioactivity of 20-31 GBq. In vitro RCP remained >96% up to 8 hours. A 370 MBq dose of 18F-TFB was administered to the subject via intravenous injection at the start of a 45-min cardiac dynamic PET/CT scan. Two additional PET/CT imaging procedures, from the vertex of the skull to mid-thigh, were performed at 2 hours and 3.5 hours respectively. Urine was collected after each PET/CT scan, and blood samples were collected throughout the study for metabolite analysis using HPLC analysis. All PET images were reconstructed using 3D OSEM and time-of-flight reconstruction. Volumes of interest (VOI’s) of the organs were drawn using PMOD software (Ver. 3.5). SUVs were then calculated for each VOI, along with time-activity curves (TACs) to monitor the pharmacokinetics of the TFB radiotracer. Radiation dosimetry estimates were calculated from scaled organ residence times using OLINDA software (Ver. 1.1), assuming a bladder voiding interval of 3.5 hours.
Results: Subjects reported no adverse events during the study. A low level of defluorination was indicated by low bone accumulation of 18F-radioactivity. High SUVs were noted in the thyroid, lacrimal glands, stomach, kidneys, and bladder. The dose-critical organ was thyroid with effective dose of 0.015 ± 0.01 mSv/MBq in all subjects. Total body effective doses were 0.061 ± 0.042 mSv/MBq in males and 0.064 ± 0.021 mSv/MBq in females.
Conclusion: 18F-TFB showed a biodistribution pattern consistent with other iodide analogs and cleared mainly through the urinary system. Radiation dosimetry estimates were on par with other 18F-radiotracers with highest exposure to thyroid. Low metabolic defluorination of 18F-TFB also supports further clinical applications for NIS imaging.