Synthesis and autoradiographic localization of muscarinic cholinergic antagonist (+)N-[C-11]methyl-3-piperidyl benzilate as a potent radioligand for positron emission tomography

(+)N-[C-11]methyl-3-piperidyl benzilate, a relatively low affinity muscarin ic cholinergic receptor antagonist was synthesized by N-[C-11]methylation o f (+)3-piperidyl benzilate using [C-11]methyl iodide. The product was isola ted by HPLC, and obtained with radiochemical yield of 60-70% from [C-11]met hyl iodide, and a specific activity of 500-1000 Ci mmol(-1) (18.5-37 GBq mu mol(-1)) at EOS and radiochemical purity of >98%. In vitro autoradiographi c studies showed selective binding for this radiotracer in the different re gions of the rat brain: high in corpus striatum, hippocampus and cerebral c ortex, and low in cerebellum, consistent with muscarinic cholinergic recept or distributions. This radiotracer thus had potential as radioligand for po sitron emission tomography. (C) 1999 Elsevier Science Ltd. All rights reser ved.