Synthesis and evaluation of 11C- and 18F-labeled 1-[2-(4-alkoxy-3-methoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazines as sigma receptor ligands for positron emission tomography studies

We prepared sigma(1)-receptor selective 1-([4-methoxy-C-11]-3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([C-11]SA4503) and its fluorinated analog 1-([4-methoxy-C-11]3,4-dimethoxyphenethyl)-4-[3-(4-fluorophenyl)propyl]piperazine ([C-11]SA5845), and their [C-11]ethoxy and [F-18]fluoroethoxy analogs, and evaluated their potential for positron emission tomography studies. [C-11]SA4503 is most selective for sigma(1) receptors. and the other five showed affinities for sigma(1) and sigma(2) receptors with a different extent. All radioligands showed the receptor-specific binding in the brain, and Visualized similar regional brain distributions by ex vivo autoradiography. The [C-11]ethoxy analogs were relatively labile for metabolism. (C) 2003 Elsevier Science Inc. All rights reserved.