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-(11)C]-3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([(11)C]SA4503) and its fluorinated analog 1-([4-methoxy-(11)C]3,4-dimethoxyphenethyl)-4-[3-(4-fluorophenyl)propyl]piperazine ([(11)C]SA5845), and their [(11)C]ethoxy and [(18)F]fluoroethoxy analogs, and evaluated their potential for positron emission tomography studies. [(11)C]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 [(11)C]ethoxy analogs were relatively labile for metabolism.