Biodistribution and Radiation Dosimetry of Deuterium- Substituted 18F-Fluoromethyl-[1, 2-2H4]Choline in Healthy Volunteers

11C-choline and 18F-fluoromethylcholine (18F-FCH) have been used in patients to study tumor metabolic activity in vivo; however, both radiotracers are readily oxidized to respective betaine analogs, with metabolites detectable in plasma soon after injection of the radio-tracer. A more metabolically stable FCH analog, 18F-fluoromethyl-[1,2-2H4]choline (18F-D4-FCH), based on the deuterium isotope effect, has been developed. We report the safety, biodistribution, and internal radiation dosimetry profiles of 18F-D4-FCH in 8 healthy human volunteers. Methods: 18F-D4-FCH was intravenously ad-ministered as a bolus injection (mean 6 SD, 161 6 2.17 MBq; range, 156–163 MBq) to 8 healthy volunteers (4 men, 4 women). Whole-body (vertex to mid thigh) PET/CT scans were acquired at 6 time points, up to 4 h after tracer injection. Serial whole-blood, plasma, and urine samples were collected for radioactivity measurement and plasma radiotracer metabolites. Tissue 18F radioactivities were determined from quantitative analysis of the images, and time–activity curves were generated. The total numbers of disintegrations in each organ normal-ized to injected activity (residence times) were calculated as the area under the curve of the time–activity curve normalized to injected ac-tivities and standard organ volumes. Dosimetry calculations were per-formed using OLINDA/EXM 1.1. Results: The injection of 18F-D4-FCH was well tolerated in all subjects, with no radiotracer-related serious adverse event reported. The mean effective dose averaged over both men and women (6SD) was estimated to be 0.025 6 0.004 (men, 0.022 6 0.002; women, 0.027 6 0.002) mSv/MBq. The 5 organs re-ceiving the highest absorbed dose (mGy/MBq) were the kidney