Radiation dosimetry and biodistribution of [18F]PF-05270430, a radiotracer for phosphodiesterase 2A (PDE2A) in rhesus macaques and humans

1012 Objectives: We report the results of a series of dynamic whole-body positron emission tomography (PET) studies performed in rhesus macaques and healthy human subjects for assessment of in vivo biodistribution and radiation dosimetry of [18F]PF-05270430, a radiotracer for phosphodiesterase 2A (PDE2A). Whole body PET imaging with [18F]PF-05270430 was conducted in one female (7.9 kg) and one male (12.2 kg) rhesus monkey. Immediately following a bolus intravenous injection of [18F]PF-05270430 (337 ± 46 MBq), a series of 20 or 17 whole-body 3D PET scans with 4 or 5 bed positions, respectively were obtained continuously over about 4 hours on a Siemens mCT scanner. Additionally, four healthy human volunteers (two males and two females) received a single bolus i.v. of up to 185 MBq of [18F]PF-05270430. Following the injection, whole body PET imaging occurred on a Siemens ECAT HR+ scanner for a period of about 6 hours. Safety and tolerability was assessed through all study visits including blood and urine samples for laboratory tests, ECGs, physical examination, neurological examination and assessments for adverse events. Whole body biodistribution, radiation absorbed dose and effective dose of [18F]PF-05270430 were evaluated for several organs and total body. Brain, heart, liver, gallbladder, intestines, kidneys, and urinary bladder were identified as source organs. In rhesus, organs with highest [18F]PF-05270430 uptake included liver, stomach, intestine, and urinary bladder. Radiotracer was eliminated primarily via hepatobiliary pathways. Significant secondary elimination via renal route was observed in the female rhesus. Gastrointestinal tract received the highest radiation dose in the male model. In the female model the highest dose was received by urinary bladder. The whole-body effective dose (ICRP-60) was 2.31E-02 mSv/MBq for female and 2.04E-02 mSv/MBq for male, similar to other 18F labeled radiopharmaceuticals. In humans, the tracer was eliminated primarily via hepatobiliary route, with a secondary elimination via urinary route. The average whole body effective dose (ED) across the 4 subjects was determined to be 3.49E-02 ± 7.59E-03 mSv/MBq, where the critical organ was determined to be the gallbladder. Based on the ED from the four healthy human volunteers, the total number of [18F]PF-05270430 scans would conservatively be limited to 6 per year for both males and females based on an injected dose of 185 MBq.