N-(6- 18F-Fluorohexyl)- N-Methylpropargylamine: A Fluorine-18-Labeled Monoamine Oxidase B Inhibitor for Potential Use in PET Studies

Abstract

We have synthesized N-(6- 18F-fluorohexyl)- N-methylpropargylamine ( 18F-FHMP) as a positron emission tomography (PET) radiotracer for monoamine oxidase B (MAO-B). The radiosynthesis was carried out by a fluorine-for-bromine substitution in 30–40% radiochemical yield in specific activities of 1–2 Ci/μmol. Selectivity for MAO-B was demonstrated by the high affinity of ( R)-deprenyl (IC 50 = 6.8 nM) and lower affinity of clorgyline (IC 50 = 1.2 μM) for the inhibition of 18F-FHMP binding in vitro in rat brain homogenates. In vitro autoradiographic studies in rat brain slices showed localization of 18F-FHMP in regions such as the ependyma of the lateral ventricle, dorsal raphe, area postrema, and other regions such as the cerebellum. The specific binding observed in the autoradiograms was displaced by preincubation with ( R)-deprenyl. In in vivo experiments, the uptake of 18F-FHMP in the rat brains was high (0.10–0.20% injected dose/g). The binding of 18F-FHMP in the rat brain correlated with the general distribution of MAO-B and was displaced completely by preadministration of 10 μM ( R)-deprenyl. These results suggest that 18F-FHMP is a potential PET radiotracer for MAO-B for use in in vitro and in vivo experiments.