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

C-11-choline and F-18-fluoromethylcholine (F-18-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 radiotracer. A more metabolically stable FCH analog, F-18-fluoromethyl[1,2-H-2(4)] choli ne (F-18-D4-FCH), based on the deuterium isotope effect, has been developed. We report the safety, biodistribution, and internal radiation dosimetry profiles of F-18-D4-FCH in 8 healthy human volunteers. Methods: F-18-D4-FCH was intravenously administered as a bolus injection (mean +/- SD, 161 +/- 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 F-18 radioactivities were determined from quantitative analysis of the images, and time-activity curves were generated. The total numbers of disintegrations in each organ normalized to injected activity (residence times) were calculated as the area under the curve of the time-activity curve normalized to injected activities and standard organ volumes. Dosimetry calculations were performed using OLINDA/EXM 1.1. Results: The injection of F-18-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 (+/- SD) was estimated to be 0.025 +/- 0.004 (men, 0.022 +/- 0.002; women, 0.027 +/- 0.002) mSv/MBq. The 5 organs receiving the highest absorbed dose (mGy/MBq) were the kidneys (0.106 +/- 0.03), liver (0.094 +/- 0.03), pancreas (0.066 +/- 0.01), urinary bladder wall (0.047 +/- 0.02), and adrenals (0.046 +/- 0.01). Elimination was through the renal and hepatic systems. Conclusion: F-18-D4-FCH is a safe PET radiotracer with a dosimetry profile comparable to other common F-18 PET tracers. These data support the further development of F-18-D4-FCH for clinical imaging of choline metabolism.