Add time:08/08/2019 Source:sciencedirect.com
We have synthesized N-[3-(2′,4′-dichlorophenoxy)-2-18F-fluoropropyl]-N-methylpropargylamine (18F-fluoroclorgyline) as a potential positron emission tomography (PET) radiotracer for monoamine oxidase A (MAO-A). The radiosynthesis was carried out by a 18F-fluoride-for-mesylate substitution reaction in approximately 20% radiochemical yield in specific activities of 1–2 Ci/μmol. Selectivity for MAO-A was demonstrated by the high affinity of clorgyline ( IC50=39 nM) and lower affinity of (R)-deprenyl ( IC50 ≥ 100 μM) for the inhibition of 18F-fluoroclorgyline binding in vitro in rat brain membranes. The uptake of 18F-fluoroclorgyline in the rat brains was high (>1.0% injected dose/g). The binding of 18F-fluoroclorgyline in the rat brain correlated with the distribution of MAO-A and was inhibited by preadministration of MAO-A inhibitors, clorgyline, and Ro 41-1049, whereas (R)-deprenyl, a MAO-B blocker, had no inhibitory effect. These results suggest that 18F-fluoroclorgyline is a potential PET radiotracer for MAO-A.
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