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| Home > Publications database > Radiosynthesis and biological evaluation of [18F]R91150, a selective 5-HT2A receptor antagonistfor PET imaging |
| Home > Publications database > Radiosynthesis and biological evaluation of [18F]R91150, a selective 5-HT2A receptor antagonistfor PET imaging |
| Conference Presentation (Invited) | FZJ-2022-03654 |
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2022
Abstract: Serotonergic 5-HT2A receptors (5-HT2ARs) in cortical and forebrain regions are an important substrate for theneuromodulatory actions of serotonin in the brain. They have been implicated in the etiology of manyneuropsychiatric disorders and serve as a target for (novel) antipsychotic, antidepressant and anxiolytic drugs.Positron emission tomography (PET) imaging using suitable radioligands can be applied for in vivo quantificationof (alterations in) receptor densities and receptor occupancy for therapy evaluation [1]. The original radiosynthesisof the selective 5-HT2AR antagonist [18F]R91150 was performed in six steps, which is laborious, time-consuming,and has low RCYs of <5%, preventing widespread use of this radioligand [2]. In this work, [18F]R91150 wasprepared using late-stage Cu-mediated radiofluorination of a corresponding NBoc-protected boronic acid pinacoleester to simplify and accelerate synthesis of the radioligand. Boc-protected [18F]R91150 was prepared in a yield of10-15% (non-decay-corrected (n.d.c.), determined by radio-HPLC, n=3) within 10 min and isolated by SPE (C18cartridge). Deprotection by TFA at 80 °C for 5 min succeeded quantitatively. Isolation by analytical radio-HPLCafforded the desired 5-HT2A-radioligand [18F]R91150 in a yield of 10% (n.d.c.) after 60 min. Autoradiographicexamination of [18F]R91150 revealed discrete accumulation in specific brain areas, that was entirely replaceable bynon-radioactive R91150, altanserin and (+)-lisuride. As expected, the less 5-HT2A specific (-)-lisuride could notcompletely compete with the binding of [18F]R91150. The in-vitro evaluation of [18F]R91150 revealed the potentialof this tracer for PET imaging of 5-HT2AR status in the human brain [3]. Future studies will focus on the in vivobehaviour of [18F]R91150 and the transfer of its synthesis to an automated module for clinical applications.
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