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

Positron emission tomography (PET) using radioligandsfor the enzymemonoamine oxidase B (MAO-B) is increasingly applied as a marker forastrogliosis in neurodegenerative disorders. In the present study,a novel reversible fluorine-18 labeled MAO-B compound, [F-18]GEH200449, was evaluated as a PET radioligand in non-human primates.PET studies of [F-18]GEH200449 at baseline showed brainexposure (maximum concentration: 3.4-5.2 SUV; n = 5) within the range of that for suitable central nervous systemradioligands and a regional distribution consistent with the knownlocalization of MAO-B. Based on the quantitative assessment of [F-18]GEH200449 data using the metabolite-corrected arterialplasma concentration as input function, the Logan graphical analysiswas selected as the preferred method of quantification. The bindingof [F-18]GEH200449, as calculated based on regional estimatesof the total distribution volume, was markedly inhibited (occupancy>80%) by the administration of the selective MAO-B ligands L-deprenyl (0.5 and 1.0 mg/kg) or rasagiline (0.75 mg/kg)prior to radioligand injection. Radioligand binding was displaceableby the administration of L-deprenyl (0.5 mg/kg) at25 min after radioligand injection, thus supporting reversible bindingto MAO-B. These observations support that [F-18]GEH200449is a reversible MAO-B radioligand suitable for applied studies inhumans.

Automated summary

In this study, a novel reversible radioligand[F-18]GEH200449 for MAO-B was evaluated as a PET imaging marker in non-human primates. The PET studies demonstrated that [F-18]GEH200449 had suitable brain exposure and regional distribution consistent with the known localization of MAO-B. The binding of [F-18]GEH200449 to MAO-B was reversible and could be displaced by the administration of selective MAO-B ligands.