Description: Radiosynthesis and Biological Evaluation of [18F]R91150, a Selective 5-HT2A Receptor Antagonist for PET-Imaging

This title appears in the Scientific Report : 2021

Radiosynthesis and Biological Evaluation of [18F]R91150, a Selective 5-HT2A Receptor Antagonist for PET-Imaging

Serotonergic 5-HT2A 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 d...

Personal Name(s):	Willmann, Michael
	Hegger, Julian / Neumaier, Bernd (Corresponding author) / Ermert, Johannes
Contributing Institute:	Nuklearchemie; INM-5
Published in:	ACS medicinal chemistry letters, 12 (2021) 5, S. 738 - 744
Imprint:	Washington, DC ACS 2021
DOI:	10.1021/acsmedchemlett.0c00658
Document Type:	Journal Article
Research Program:	Decoding Brain Organization and Dysfunction
Link:	Published on 2021-04-01. Available in OpenAccess from 2022-04-01. Restricted
	Publikationsportal JuSER

Please use the identifier: http://hdl.handle.net/2128/27820 in citations.
Please use the identifier: http://dx.doi.org/10.1021/acsmedchemlett.0c00658 in citations.

Serotonergic 5-HT2A 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-HT2AR 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-HT2A receptor ligands.