PET Evaluation of the Novel F-18 Labeled Reversible Radioligand [F]GEH200449 for Detection of Monoamine Oxidase-B in the Non-Human Primate Brain.

Positron emission tomography (PET) using radioligands for the enzyme monoamine oxidase B (MAO-B) is increasingly applied as a marker for astrogliosis in neurodegenerative disorders. In the present study, a novel reversible fluorine-18 labeled MAO-B compound, [F]GEH200449, was evaluated as a PET radioligand in non-human primates. PET studies of [F]GEH200449 at baseline showed brain exposure (maximum concentration: 3.4-5.2 SUV; = 5) within the range of that for suitable central nervous system radioligands and a regional distribution consistent with the known localization of MAO-B. Based on the quantitative assessment of [F]GEH200449 data using the metabolite-corrected arterial plasma concentration as input function, the Logan graphical analysis was selected as the preferred method of quantification. The binding of [F]GEH200449, as calculated based on regional estimates of the total distribution volume, was markedly inhibited (occupancy >80%) by the administration of the selective MAO-B ligands -deprenyl (0.5 and 1.0 mg/kg) or rasagiline (0.75 mg/kg) prior to radioligand injection. Radioligand binding was displaceable by the administration of -deprenyl (0.5 mg/kg) at 25 min after radioligand injection, thus supporting reversible binding to MAO-B. These observations support that [F]GEH200449 is a reversible MAO-B radioligand suitable for applied studies in humans.