SYNTHESIS AND IN-VIVO STUDIES OF A SPECIFIC MONOAMINE-OXIDASE-B INHIBITOR - -3-(2-CYANOETHYL)-1,3,4-OXADIAZOL-[C-11]-2(3H)-ONE - BIODISTRIBUTION IN THE RAT AND POSITRON EMISSION TOMOGRAPHY STUDIES IN THE BABOON BRAIN

We report the radiochemical synthesis of a specific MAO B inhibitor, n amely -3-(2-cyanoethyl)-1,3,4-oxadiazol-[C-11]-2(3H)-one (2b) (in vitr o IC50=4nM and selectivity over 71000 for MAO B), by cyclization of it s hydrazide precursor 1 with [C-11]phosgene. The reaction occurred wit hin 2 min. The product obtained after HPLC purification, 2b, had a hig h specific activity (11.1-22.2 GBq/mu mol), allowing its use in experi ments as a radiotracer in vivo, Biodistribution of 2b in the CNS and i n the peripheral organs of the rat, and positron emission tomography ( PET) studies in the living baboon brain, pretreated or not with L-depr enyl(1 mg/kg, 1 h), an irreversible MAO B-specific inhibitor, were und ertaken. The results showed a good uptake of 2b in all organs of the r at, with a rapid clearance from the blood (10 min). Metabolite analyse s in plasma and in the diencephalon of the rat showed that 2b was the only radioactive compound in brain structure whereas in plasma three o ther radioactive products appeared. PET experiments show that in the L -deprenyl-pretreated baboon brain, specific binding of 2b represents a round 70% of total radioactivity, whereas in the blood and plasma the radioactivity cleared rapidly (15 min).