Development of a novel fluorine-18 labeled deuterated fluororasagiline ([18F]fluororasagiline-D2) radioligand for PET studies of monoamino oxidase B (MAO-B)

Abstract The objective of this study was to synthesize and evaluate a novel fluorine-18 labeled deuterium substituted analogue of rasagiline ( 9 , [ 18 F]fluororasagiline-D 2 ) as a potential PET radioligand for studies of monoamine oxidase B (MAO-B). The precursor compound ( 6 ) and reference standard ( 7 ) were synthesized in multi-step syntheses. Radiolabeling of 9 was accomplished by a two-step synthesis, compromising a nucleophilic substitution followed by hydrolysis of the sulfamidate group. The incorporation radiochemical yield from fluorine-18 fluoride was higher than 30%, the radiochemical purity was >99% and the specific radioactivity was >160 GBq/μmol at the time of administration. In vitro compound 7 inhibited the MAO-B activity with an IC 50 of 173.0 ± 13.6 nM. The MAO-A activity was inhibited with an IC 50 of 9.9 ± 1.1 μM. The fluorine-18 version 9 was characterized in the cynomolgus monkey brain where a high brain uptake was found (275% SUV at 4 min). There was a higher uptake in the striatum and thalamus compared to the cortex and cerebellum. A pronounced blocking effect (50% decrease) was observed in the specific brain regions after administration of l -deprenyl (0.5 mg/kg) 30 min prior to the administration of 9 . Radiometabolite studies demonstrated 40% of unchanged radioligand at 90 min post injection. An efficient radiolabeling of 9 was successfully established and in the monkey brain 9 binds to MAO-B rich regions and its binding is blocked by the selective MAO-B compound l -deprenyl. The radioligand 9 is a potential candidate for human PET studies.