Biodistribution and radiation dosimetry of [¹⁸F]-5-fluorouracil

To estimate the radiation dose and biodistribution of (18)F-5-fluorouracil ([(18)F]-5-FU) from positron emission tomography/computed tomography (PET/CT) data, and to extrapolate mouse data to human data in order to evaluate cross-species consistency.

Fifteen cancer patients (head and neck cancer (n=11), colon cancer (n=4)) were enrolled. Sequential PET/CT images were acquired for 2h after intravenous administration of [(18)F]-5-FU, and the percent of the injected dose delivered to each organ was derived. For comparison, [(18)F]-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.

In human subjects, high [(18)F]-5-FU uptake was seen in the liver, gallbladder and kidneys. The absorbed dose was highest in the gallbladder wall. In mice, the biodistribution of [(18)F]-5-FU corresponded to that of humans. Estimated absorbed radiation doses for all organs were moderately correlated, and doses to organs (except the gallbladder and urinary bladder) were significantly correlated between mice and humans. The mean effective [(18)F]-5-FU dose was higher in humans (0.0124mSv/MBq) than in mice (0.0058mSv/MBq).

Biodistribution and radiation dosimetry of [(18)F]-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 [(18)F]-5-FU PET/CT for human studies.