Whole-body radiation dosimetry of 11C-carbonyl-URB694: a PET tracer for fatty acid amide hydrolase.

Abstract

(11)C-carbonyl-URB694 ((11)C-CURB) is a novel (11)C-labeled suicide irreversible radiotracer for PET developed as a surrogate measure of activity of the endocannabinoid metabolizing enzyme fatty acid amide hydrolase. The aim of the study was to investigate the whole-body biodistribution and estimate the radiation dosimetry from (11)C-CURB scans in humans. Six healthy volunteers (3 men and 3 women) completed a single whole-body scan (∼120 min, 9 time frames) on a PET/CT scanner after administration of (11)C-CURB (∼350 MBq and ∼2 μg). Time-radioactivity curves were extracted in 11 manually delineated organs and corrected for injected activity, specific organ density, and volume to obtain normalized cumulated activities. OLINDA/EXM 1.1 was used to estimate standard internal dose exposure in each organ. The mean effective dose was calculated using the male and female models for the full sample and female-only sample, respectively. (11)C-CURB was well tolerated in all subjects, with no radiotracer-related adverse event reported. The mean effective dose (±SD) was estimated to be 4.6 ± 0.3 μSv/MBq for all subjects and 5.2 ± 0.3 μSv/MBq for the female sample. Organs with the highest normalized cumulated activities (in h) were the liver (0.117), gallbladder wall (0.046), and small intestine (0.033), and organs with the highest dose exposure (in μGy/MBq) were the gallbladder wall (111 ± 60) > liver (21 ± 7), kidney (14 ± 3), and small intestine (12 ± 2). Organ radiation exposure for the irreversible fatty acid amide hydrolase enzyme probe (11)C-CURB is within the same range as other radiotracers labeled with (11)C, thus allowing for safe, serial PET scans in the same individuals.