Synthesis and characterization of 11C-labeled fluoroclorgyline: a monoamine oxidase A specific inhibitor for positron emission tomography.

A new radioligand for monoamine oxidase type A (MAO-A), [11C]fluoroclorgyline, was synthesized from its desmethyl precursor by N-methylation reaction using [11C]methyl iodide with a radiochemical yield of 75-85%. The radiochemical purity of the product was more than 99% and the specific radioactivity was 7.4-18.5 GBq/micromol. The in vivo tissue distribution studies of [11C]fluoroclorgyline in mice demonstrated its high initial uptake and prolonged retention in the brain, comparable to those of [11C]clorgyline. A selective interaction with MAO-A in the accumulation of [11C]fluorclorgyline was confirmed by a competition experiment performed with the MAO-A specific inhibitor,clorgyline, and MAO-B specific inhibitor, l-deprenyl. These very desirable characteristics of [11C]fluoroclorgyline suggested that its 18F labeled counterpart, [18F]fluoroclorgyline, would have great potential as a longer-lived alternative to 11C labeled clorgyline for in vivo studies of MAO-A in the human brain with positron emission tomography (PET).