DESIGN AND EVALUATION OF RADIOACTIVE ACETYLCHOLINE ANALOGS FOR MAPPING BRAIN ACETYLCHOLINESTERASE (ACHE) IN-VIVO

For mapping brain acetylcholinesterase (AchE) in vivo, seven radioactive acetylcholine analogs, N-[C-14]methylpiperidyl-3- and 4-acetates, propionates, isobutyrates, and 3-butyrate were newly synthesized and evaluated in mice. The esters readily entered the brain and were hydrolyzed into the hydrophilic metabolite, which was trapped. In brain homogenates, the esters showed a wide range of enzymatic reactivity (about 40-fold), and high specificity for AchE (more than 82%) except the butyrate. Intra-brain distribution of the esters reflected a pattern of AchE activity.