[C-11]N-methylhomoepibatidine: Radiolabelling and biodistribution studies in mice.

The radiochemical synthesis of [C-11]N-methylhomoepibatidine (2) was accomp lished by reacting homoepibatidine (1) and [C-11]iodomethane. The radiochem ical yield was in the range of 5 to 10 % related to [C-ll]iodomethane. A hi gh specific activity of 150 to 370 GBq/mu mol at the end of synthesis was a chieved. The partition coefficient was log P-7.4 = 0.34. Biological evaluat ion was performed with the racemate in mice. High brain uptake was found. C ompared to [C-11]N-methylepibatidine (4) data, which were achieved by the s ame experimental setup, the values of [C-11]N-methylhomoepibatidine (2) upt ake in the brain were slightly lower (approximately 15 %/g compared to 20 % /g for [C-11]N-methylepibatidine (4)). But in contrast to the homologous [C -11]N-methylepibatidine (4) the brain uptake curve decreased after approxim ately 15 minutes showing reversible binding to the receptor. Pretreatment o f mice with (-)-epibatidine (3) resulted in a considerably lower brain upta ke while uptake in other tissues remained unchanged.