Synthesis and in vitro autoradiographic evaluation of a novel high-affinity radioiodinated ligand for imaging brain cannabinoid subtype-1 receptors

Abstract

There is strong interest to study the involvement of brain cannabinoid subtype-1 (CB 1) receptors in neuropsychiatric disorders with single photon emission computed tomography (SPECT) and a suitable radioligand. Here we report the synthesis of a novel high-affinity radioiodinated CB 1 receptor ligand ([ 125I] 8, [ 125I]1-(2-iodophenyl)-4-cyano-5-(4-methoxyphenyl)- N-(piperidin-1-yl)-1 H-pyrazole-3-carboxylate, [ 125I]SD7015). By autoradiography in vitro, [ 125I] 8 showed selective binding to CB 1 receptors on human brain postmortem cryosections and now merits labeling with iodine-123 for further evaluation as a SPECT radioligand in non-human primate.