Synthesis and preliminary evaluation of [18F]FEtP4A, a promising PET tracer for mapping acetylcholinesterase in vivo

N-[F-18]Fluoroethyl-4-piperidyl acetate ([F-18]FEtNA), an analog of [C-11]MP4A for mapping brain acetylcholineseterase (AchE) activity, was prepared by reacting 4-piperidyl acetate (P4A) with [F-18]fluoroethyl bromide ([F-18]FEtBr) using a newly developed automated system. Preliminary evaluation showed that the initial uptake of [F-18]FF-tP4A in the mouse brain was > 8% injected dose/g tissue. The distribution pattern of [F-18]FEtP4A in the brain was striatum> cerebral cortex >cerebellum within 10-120 min post-injection, which reflected the distribution rank pattern of AchE activity in the brain. Moreover, chemical analysis of in vivo radioactive metabolites in the mouse brain indicated that 83% of [F-18]FEtP4A was hydrolyzed to N-[F-18]fluoroethyl-4-piperidinol ([F-18]FEtP4OH) after 1 min intravenous injection. From these results, [F-18]FEtP4A may become a promising PET tracer for mapping the AchE in vivo. (C) 2002 Elsevier Science Inc. All rights reserved.