Autoradiographic Evaluation of [¹⁸F]FECUMI-101, a High Affinity 5-HT_1AR Ligand in Human Brain

[¹⁸F]FECUMI-101 ([¹⁸F]1) is a 5HT_1AR ligand demonstrating specific binding in brain regions corresponding to the distribution of 5-HT_1AR in baboons. However, we detected moderate uptake of [¹⁸F]1 in baboon thalamus, a brain region lacking 5-HT_1AR. We sought to investigate the relative binding of [¹⁸F]1 to 5-HT_1AR, α₁R, and 5-HT₇R in vitro. Using autoradiography in human brain sections, specific binding of [¹⁸F]1 to 5-HT_1AR was confirmed. However, [¹⁸F]1 also showed 26% binding to α₁R in PFC. The hippocampal formation exhibited 51% and 92% binding of [¹⁸F]1 to α₁R and 5-HT_1AR, respectively. Thalamus and cerebellum showed very little binding. There is no measurable specific binding of [¹⁸F]1 to 5-HT₇R and no effect of temperature on [¹⁸F]1 specific binding to 5-HT_1AR or α₁R. These results indicate that, while [¹⁸F]FECUMI-101 is not a completely selective 5-HT_1AR ligand for receptor quantification, it may be useful for occupancy measurements of drugs acting at 5-HT_1AR in vivo.