Synthesis, radiofluorination and preliminary evaluation of the potential 5-HT2A receptor agonists [18F]Cimbi-92 and [18F]Cimbi-150

An agonist PET tracer is of key interest for the imaging of the 5-HT2A receptor, as exemplified by the previously reported success of [11C]Cimbi-36. Fluorine-18 holds several advantages over carbon-11, making it the radionuclide of choice for clinical purposes. In this respect, a 18F-labelled agonist 5-HT2A receptor (5-HT2AR) tracer is highly sought after. Herein we report a two-step, one-pot labelling methodology of two tracer candidates. Both ligands display high in vitro affinities for the 5-HT2AR. The compounds were synthesised from easily accessible labelling precursors, and radiolabelled in acceptable radiochemical yields, sufficient for in vivo studies in domestic pigs. PET images partially conformed to the expected brain distribution of the 5-HT2AR; a notable exception however being significant uptake in the striatum and thalamus. Additionally, a within-scan displacement challenge with a 5-HT2AR antagonist was unsuccessful, indicating that the tracers cannot be considered optimal for neuroimaging of the 5-HT2AR.