Radiosynthesis and Biological Evaluation of [¹⁸F]R91150, a Selective 5-HT_2A Receptor Antagonist for PET-Imaging

Serotonergic 5-HT_2A receptors in cortical and forebrain regions are an important substrate for the neuromodulatory actions of serotonin in the brain. They have been implicated in the etiology of many neuropsychiatric disorders and serve as a target for antipsychotic, antidepressant, and anxiolytic drugs. Positron emission tomography imaging using suitable radioligands can be applied for in vivo quantification of receptor densities and receptor occupancy for therapy evaluation. Recently, the radiosynthesis of the selective 5-HT_2AR antagonist [¹⁸F]R91150 was reported. However, the six-step radiosynthesis is cumbersome and time-consuming with low radiochemical yields (RCYs) of <5%. In this work, [¹⁸F]R91150 was prepared using late-stage Cu-mediated radiofluorination to simplify its synthesis. The detailed protocol enabled us to obtain RCYs of 14 ± 1%, and the total synthesis time was reduced to 60 min. In addition, autoradiographic studies with [¹⁸F]R91150 in rat brain slices revealed the typical uptake pattern of 5-HT_2A receptor ligands.