Autoradiographic evaluation of [³H]CUMI-101, a novel, selective 5-HT_1AR ligand in human and baboon brain

[¹¹C]CUMI-101 is the first selective serotonin receptor (5-HT_1AR) partial agonist radiotracer for positron emission tomography (PET) tested in vivo in nonhuman primates and humans. We evaluated specific binding of [³H]CUMI-101 by quantitative autoradiography studies in postmortem baboon and human brain sections using the 5-HT _1AR antagonist WAY-100635 as a displacer. The regional and laminar distributions of [³H]CUMI-101 binding in baboon and human brain sections matched the known distribution of [³H]8-OH-DPAT and [ ³H]WAY-100635. Prazosin did not measurably displace [ ³H]CUMI-101 binding in baboon or human brain sections, thereby ruling out [³H]CUMI-101 binding to α1-adrenergic receptors. This study demonstrates that [¹¹C]CUMI-101 is a selective 5-HT _1AR ligand for in vivo and in vitro studies in baboon and human brain.