Abstract
1019
Objectives An 18F labeled exendin-4 has been developed for pancreatic islet imaging by targeting the glucagonlike peptide-1 receptor. We measured the biodistribution of 18F-TTCO-Cys40-Exendin-4 in a non-human-primate and used it to estimate the radiation dosimetry for humans.
Methods A male, adult cynomolgus macaque monkey was scanned with PET/CT on 4 separate days, each time after a 12 h fast. Multiple sweeps (approximately 100 min each) were acquired to obtain time-activity-curves (TACs) for whole body and multiple organs. Integral time-activity (area under the curve, AUC) was calculated for each non-decay corrected TAC. Organ residence times were then calculated as AUC/initial total body activity. The Organ Level Internal Dose Assessment (OLINDA) software was used to calculate whole body, organ and tissue absorbed doses per injected activity for male and female subjects.
Results 18F-TTCO-Cys40-Exendin-4 was well tolerated by the monkey, with no changes in vital signs during the scans. There was noticeable accumulation of tracer in liver, kidneys, heart, small intestines and bladder. The critical organ is, by far, the bladder, with estimated absorbed doses of 0.16 and 0.24 mGy/MBq respectively for male and female human adults. The effective dose is 0.020 and 0.028 mSv/MBq, respectively, for males and females.
Conclusions Single study maximum radiation dose from 18F-TTCO-EX4 will remain below the 21 CFR 361.1 limit for research subjects provided injected activities are ≤ 0.12 mCi/kg for males and 0.098 mCi/kg for females (calculation based on bladder as critical organ, ≤ 3 rad/study for whole body, active blood forming organs, lens of the eyes and gonads, and ≤ 5 rad/study for other organs). The maximum annual radiation dose limit (15 rad) corresponds to injected activities of 0.36 mCi/kg for males and 0.29 mCi/kg for females.