Autoradiographic evaluation of [3H]CUMI-101, a novel, selective 5-HT1AR ligand in human and baboon brain

[11C]CUMI-101 is the first selective serotonin receptor (5-HT1AR) 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-HT1AR 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-HT1AR ligand for in vivo and in vitro studies in baboon and human brain. ► [3H]CUMI-101 binding is consistent with known distribution of 5-HT1AR. ► The in vitro binding data of [3H]CUMI-101 is in agreement with [3H]8-OH-DPAT. ► The in vitro data of [3H]CUMI-101 is comparable with in vivo data of [11C]CUMI-101.