18F-Nifene: Efficacy as PET imaging agent of Nicotinic α4β2 Receptors from Mice to Humans

490 Objectives We have developed the agonist 18F-nifene for PET imaging studies of nicotinic α4β2 receptors in various CNS disorders. Upon successful completion of rodent and monkey studies, we report comparative brain distribution of 18F-nifene in humans. Methods Radiosyntheses of 18F-nifene was carried out with high specific activity 18F-fluoride as reported previously. Rodent, monkey and human studies were carried out either on an Inveon MicroPET/CT, MicroPET P4, or Siemen’s HR+ scanner. Human 18F-nifene studies were carried out under an FDA approved IND. All studies were carried out after an IV bolus injection of 18F-nfiene (~0.2 mCi for mice, ~0.7 mCi for rats, ~2-3 mCi for monkeys, ~5 mCi for humans) at a specific activity >2Ci/mmol. Isoflurane anesthesia (1.5-3%) was used for rodents and monkeys. Binding of 18F-nifene to α4β2 receptor-rich regions were analyzed using ASIPro and PMOD. Results Rapid brain uptake of 18F-nifene was observed in all brain regions across all species. Cerebellum (CB) was used as a reference region across all species, except humans. For humans, corpus callosum (CC) was used as a reference region. Thalamus (TH) exhibited the highest levels of 18F-nifene uptake with a time of pseudo equilibrium, indicated by plateau of target/reference curves, of ~45mins across all species. Extrathalamic uptake in regions such as cortical areas, lateral geniculate, cingulate gyrus and other brain regions were observed in all species and consistent with the reported levels of α4β2 receptors. At equilibrium, 18F-nifene exhibited ratios of: TH/CC~3 (humans), TH/CB~3 (monkeys, rats and mice). Conclusions 18F-Nifene appears to be a safe, stable, selective and effective α4β2 nicotinic receptor imaging agent in animal models and humans. Our findings with 18F-nifene suggest homology of the α4β2 receptor-site across species. 18F-Nifene therefore may be reliably used to quantify α4β2 receptor distribution in brain regions for the translational study of various CNS disorders. Research Support NIH R01AG029479