000910174 001__ 910174
000910174 005__ 20221209131503.0
000910174 037__ $$aFZJ-2022-03654
000910174 041__ $$aEnglish
000910174 1001_ $$0P:(DE-Juel1)131818$$aErmert, Johannes$$b0$$eCorresponding author$$ufzj
000910174 1112_ $$aDPhG Annual Meeting 2022$$cMarburg$$d2022-09-14 - 2022-09-16$$gDPhG 2022$$wGermany
000910174 245__ $$aRadiosynthesis and biological evaluation of [18F]R91150, a selective 5-HT2A receptor antagonistfor PET imaging
000910174 260__ $$c2022
000910174 3367_ $$033$$2EndNote$$aConference Paper
000910174 3367_ $$2DataCite$$aOther
000910174 3367_ $$2BibTeX$$aINPROCEEDINGS
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000910174 3367_ $$0PUB:(DE-HGF)6$$2PUB:(DE-HGF)$$aConference Presentation$$bconf$$mconf$$s1670586993_28873$$xInvited
000910174 520__ $$aSerotonergic 5-HT2A receptors (5-HT2ARs) in cortical and forebrain regions are an important substrate for theneuromodulatory actions of serotonin in the brain. They have been implicated in the etiology of manyneuropsychiatric disorders and serve as a target for (novel) antipsychotic, antidepressant and anxiolytic drugs.Positron emission tomography (PET) imaging using suitable radioligands can be applied for in vivo quantificationof (alterations in) receptor densities and receptor occupancy for therapy evaluation [1]. The original radiosynthesisof the selective 5-HT2AR antagonist [18F]R91150 was performed in six steps, which is laborious, time-consuming,and has low RCYs of <5%, preventing widespread use of this radioligand [2]. In this work, [18F]R91150 wasprepared using late-stage Cu-mediated radiofluorination of a corresponding NBoc-protected boronic acid pinacoleester to simplify and accelerate synthesis of the radioligand. Boc-protected [18F]R91150 was prepared in a yield of10-15% (non-decay-corrected (n.d.c.), determined by radio-HPLC, n=3) within 10 min and isolated by SPE (C18cartridge). Deprotection by TFA at 80 °C for 5 min succeeded quantitatively. Isolation by analytical radio-HPLCafforded the desired 5-HT2A-radioligand [18F]R91150 in a yield of 10% (n.d.c.) after 60 min. Autoradiographicexamination of [18F]R91150 revealed discrete accumulation in specific brain areas, that was entirely replaceable bynon-radioactive R91150, altanserin and (+)-lisuride. As expected, the less 5-HT2A specific (-)-lisuride could notcompletely compete with the binding of [18F]R91150. The in-vitro evaluation of [18F]R91150 revealed the potentialof this tracer for PET imaging of 5-HT2AR status in the human brain [3]. Future studies will focus on the in vivobehaviour of [18F]R91150 and the transfer of its synthesis to an automated module for clinical applications.
000910174 536__ $$0G:(DE-HGF)POF4-5253$$a5253 - Neuroimaging (POF4-525)$$cPOF4-525$$fPOF IV$$x0
000910174 7001_ $$0P:(DE-Juel1)173964$$aWillmann, Michael$$b1
000910174 7001_ $$0P:(DE-Juel1)166419$$aNeumaier, Bernd$$b2$$ufzj
000910174 8564_ $$uhttps://juser.fz-juelich.de/record/910174/files/Abstract-Vorlage%20DPhG%20Ermert.pdf$$yRestricted
000910174 8564_ $$uhttps://juser.fz-juelich.de/record/910174/files/acsmedchemlett.0c00658.pdf$$yRestricted
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000910174 9141_ $$y2022
000910174 920__ $$lyes
000910174 9201_ $$0I:(DE-Juel1)INM-5-20090406$$kINM-5$$lNuklearchemie$$x0
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