Biodistribution and radiation dosimetry of [18F]-5-fluorouracil: A comparison of human and mouse data

Objectives The purpose of this study is to estimate the radiation dose associated with 18F-labeled 5-fluorouracil ([18F]5-FU), and to assess its biodistribution and pharmacokinetics from PET/CT imaging data. We also extrapolated animal experimental data to human model, to evaluate the consistency across the species.

Methods Fifteen cancer patients (head and neck cancer (n=11), colon cancer (n=4)) were enrolled. Sequential PET/CT images were acquired for 2 hours after intravenous administration of [18F]-5-FU, and the percent of the injected dose delivered to each organ was derived. For comparison, [18F]-5-FU was administered to female BALB/cAJcl-nu/nu nude mice (n=19), and the percent of the injected dose delivered to mouse organs was extrapolated to the human model. Absorbed radiation dose was calculated using OLINDA/EXM 1.0 software.

Results In the human subject, blood level of [18F]5-FU decreased immediately after injection, and high uptake of [18F]5-FU was shown in liver, gallbladder and kidneys. Absorbed dose was highest in gallbladder wall, followed by liver, urinary bladder wall and kidney. In mouse, the biodistribution of [18F]5-FU was corresponded to human, but organ radiation doses were underestimated. Estimated absorbed radiation doses of all organs showed moderate correlation, and doses of organs except for gallbladder and urinary bladder showed significant correlation between mouse and human. The mean effective dose for [18F]5-FU was 0.0124mSv/MBq in human and 0.0058mSv/MBq in mouse.

Conclusions Biodistribution and radiation dosimetry of [18F]-5-FU were compared between humans and mice: biodistribution in mice and humans was similar. Data from mice underestimated the effective dose in humans, suggesting that clinical measurements are needed for more detailed dose estimation in order to ensure radiation safety. The observed effective doses suggest the feasibility of [18F]-5-FU PET/CT for human studies