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 sigma1-receptor selective 1-([4-methoxy-11C]-3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([11C]SA4503) and its fluorinated analog 1-([4-methoxy-11C]3,4-dimethoxyphenethyl)-4-[3-(4-fluorophenyl)propyl] piperazine ([11C]SA5845), and their [11C]ethoxy and [18F]fluoroethoxy analogs, and evaluated their potential for positron emission tomography studies. [11C]SA4503 is most selective for sigma1 receptors, and the other five showed affinities for sigma1 and sigma2 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 [11C]ethoxy analogs were relatively labile for metabolism