SYNTHESIS OF + --[F-18]BMY 14802, ITS ENANTIOMERS AND THEIR ANATOMICAL DISTRIBUTIONS IN RODENTS/

A potential antipsychotic drug, BMY 14802 was labeled with F-18 and it s distribution in rodents was studied. No-carrier-added (NCA) (+/-)-[F -18]BMY 14802 (5) was synthesized by two methods in 5-10% radiochemica l yield in a synthesis time of 130 140 min from EOB with a specific ac tivity of 0.5-1.5 Ci/muM. (+)- and (-)-[F-18]BMY 14802 was synthesized by the chiral reduction of )-4-(5-fluoro-2-pyrimidinyl)-1-piperazine- butanone (4) with chiral reducing agent, (+)- and (-)-beta-chlorodiiso pinocampheylborane [(+)- and (-)-DIP chloride] in 6-10% radiochemical yield in a synthesis time of 150 min from EOB. Animal studies in mouse and in rat revealed that the distribution of 5 in each tissue was hig h at 5 min, the radioactivity then declined rapidly in all tissues stu died except in the liver and in the small intestine. The radioactivity in the femur did not increase with time indicating in vivo defluorina tion may not occur. The uptakes of (+/-)-[F-18]BMY 14802 and its enant iomers, (+)- and (-)-[F-18]BMY 14802 in rat cerebellum, brain stem, hi ppocampus and spinal cord were similar and were significantly reduced by prior treatment of rat with haldol. This suggests that (+/-)-[F-18] BMY 14802 and its enantiomers bind to sigma-receptors in a similar fas hion.