Preclinical Safety Evaluation and Non-Human Primates Dosimetry of [18F]AS3504073-00, a Novel Positron Emission Tomography (PET) Ligand for Fatty-Acid Oxidation (FAO).

1023 Purpose: [18F]AS3504073-00 is a novel, metabolic-trapping positron emission tomography (PET) ligand for fatty-acid oxidation (FAO), a potential marker for addressing heart disease status. The present research provides fundamental information from preclinical toxicity studies in rats and dosimetry studies of [18F]AS3504073-00 in non-human primates for its potential application in upcoming human studies. Methods: AS3504073-00 was intravenously administered (IV) in a 7-day rat toxicity study at × 100 dose margins relative to projected highest clinical dose of 0.333 μg/kg. Whole-body PET scans were performed in 3 male cynomolgus monkeys after IV bolus injection of [18F]AS3504073-00 to characterize organ distribution and to estimate radiation exposure (effective dose). Results: AS3504073-00 administered IV in a 7-day rat toxicity study did not show any test article-related changes. The no-observed-adverse-effect level in rats was ≥ 33.3 μg/kg/day which provides a margin 100-fold over an anticipated maximum clinical dose of 0.333 μg/kg. [18F]AS3504073-00 showedhighest organ absorbed doses for the urinary bladder wall (119 μGy/MBq). The effective dose was 19.1 μSv/MBq. Conclusions: [18F]AS3504073-00 would be tolerable for clinical PET imaging studies.