Monoamine oxidase B in the brain is predominantly expressed in astrocytes and increased MAO-B activity has been proposed as a biomarker of gliosis. Prior successful imaging agents for MAO-B have been based on the reaction of irreversible inhibitors, such as [11C]deprenyl and related radiotracers. The objective of this work is the synthesis and evaluation of radiolabeled non-toxic N-methyl-1,2,3,6-tetrahydropyridines that would be trapped in the brain in proportion to MAO-B catalyzed oxidation to the corresponding dihydropyridinium salts; as well as, the synthesis and evaluation 1,5-Diphenylpenta-2,4-dien-1-one competitive inhibitors. The oxidation of the dihydropyridine can produce non-toxic products provided the group substituted at the 4 position is susceptible to hydrolysis upon oxidation by MAO-B that additionally could provide a means for more favorable pharmacokinetics of the radiolabel for imaging studies. The generation of a competitive substrate or inhibitor of MAO-B should provide data not only on MAO-B expression levels but also its kinetics in vivo.

Synthesis and preliminary evaluation of radiolabeled substrates and inhibitors for in vivo monoamine oxidase B imaging

246th National Meeting (2013)

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