F-18-Mefway: Efficacy as a PET imaging agent for serotonin 5-HT1A receptors

553 Objectives Serotonin 5-HT1A receptors, implicated in CNS disorders, have been studied with 18F-trans-Mefway (18F-Mefway) in rodent and nonhuman primate studies. Following successful completion of rodent and nonhuman primate studies, we report comparative distribution of 18F-Mefway in humans. Methods Radiosynthesis of 18F-Mefway was carried out as previously reported. Human 18F-Mefway studies were carried out under an FDA approved IND. Both preclinical and clinical studies were carried out after an IV bolus injection of 18F-Mefway (~0.5 mCi for rat, 2-3 mCi for monkeys, 5 mCi for humans) with specific activity >2Ci/µmol. Isoflurane anesthesia (1.5-3%) was used for rodents and monkeys. Rodent, nonhuman primate and human studies were performed on an Inveon MicroPET/CT, MicroPET P4, and Siemen’s HR+ scanner, respectively. Using ASIPro and PMOD, analysis of 18F-Mefway binding to 5-HT1A receptor-rich regions was performed. Results Across various species rapid brain uptake of 18F-Mefway was observed in all brain regions. Cerebellum (CB) was used as a reference region in all studies across all species due to a lack of receptor specific binding. Distribution of 18F-Mefway in human brain regions was consistent with the known concentration of 5-HT1A receptors: mesial temporal cortex/ hippocampus (MTC/ HP)> insula (IN) > cingulate gyrus (CG) = dorsal raphe (DR). Human brain regions to cerebellum maximal ratios were found to be MTC/CB=7; IN/CB=5; CG/CB=3.8; DR/CB=3.5. 18F-Mefway brain uptake in humans was not hampered from bone uptake in the skull. Conclusions Ongoing PET studies in all models including humans have indicated 18F-Mefway to be efficacious as a serotonin 5-HT1A receptor imaging agent. 18F-Mefway therefore may be reliably used to quantify serotonin 5-HT1A receptor distribution in brain regions including small areas such as the DR for the study of various CNS disorders in animal models and human diseases. Research Support NIH/NIA R33AG030524