Three fluorine containing derivatives of Cimbi-36 were synthesized and found to be potent 5-HT2A agonists. 18F-labeling of the appropriate precursors was performed using [18F]FETos, typically yielding 0.2–2.0 GBq and specific activities of 40–120 GBq/μmol. PET studies in Danish landrace pigs revealed that [18F]1 displayed brain uptake in 5-HT2AR rich regions. However, high uptake in bone was also observed. No blocking effect was detected during a competition experiment with a 5-HT2AR selective antagonist. [18F]2 and [18F]3 showed very low brain uptake.
None of the investigated 18F-labeled Cimbi-36 derivatives [18F]1, [18F]2 and [18F]3 show suitable tracer characteristics for in vivo PET neuroimaging of the 5-HT2AR. Although for [18F]1 there was reasonable brain uptake, we suggest that a large proportion radioactivity in the brain was due to radiometabolites, which would explain why it could not be displaced by a 5-HT2AR antagonist.