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@ARTICLE{Hoffmann:1037540,
author = {Hoffmann, Chris and Endepols, Heike and Urusova, Elizaveta
and Elchine, Dominik and Neumaier, Felix and Neumaier, Bernd
and Zlatopolskiy, Boris},
title = {[18{F}]{R}91150: {I}mproved radiosynthesis and in vivo
evaluation as imaging probe for 5-{HT}2{A} receptors},
journal = {European journal of medicinal chemistry},
volume = {286},
issn = {0009-4374},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {FZJ-2025-00729},
pages = {117265},
year = {2025},
note = {This work was supported by Deutsche Forschungsgemeinschaft
(DFG) grants ZL 65/1-1, ZL 65/3-1 and ZL 65/4-1.},
abstract = {Serotonergic 5-HT2A receptors in the cortex and other
forebrain structures have been linked to cognitive,emotional
and memory processes. In addition, dysfunction or altered
expression of these receptors is associatedwith
neuropsychiatric and neurodegenerative disorders.
[18F]R91150 is a candidate radiotracer for positronemission
tomography (PET) imaging of 5-HT2A receptors, which showed
promising properties in in vitro studies.However, existing
methods for the production of [18F]R91150 are rather
inefficient and its imaging propertieshave not been studied
in vivo. In the present work, we describe improved protocols
for preparation of[18F]R91150, the corresponding reference
compound and two alternative boronate radiolabeling
precursors.Furthermore, we present the results of an in vivo
evaluation of the radioligand in rodents. [18F]R91150
wasprepared in activity yields of 20 ± $5\%$ (two-step
radiosynthesis) or 12 ± $2\%$ (one-step radiosynthesis) and
withmolar activities of >200 GBq/μmol. μPET measurements
in mice revealed sufficient stability against in
vivodefluorination and predominantly hepatobiliary excretion
of the tracer, with high radioactivity uptake in gallbladder
and intestines. μPET imaging in rats demonstrated specific
tracer accumulation in the cortex andsubcortical forebrain
structures, which could be reduced by pretreatment or
displacement with the 5-HT2A receptorligands altanserin or
ketanserin but was insensitive to pretreatment with the
5-HT2C receptor ligandSB242084. In addition, [18F]R91150
showed specific accumulation in the choroid plexus that was
much lesssensitive to displacement with ketanserin and
unaffected by pretreatment with altanserin or SB242084.
Takentogether, our results indicate that [18F]R91150 may be
a promising candidate for in vivo PET imaging of
cortical5-HT2A receptors, although further studies will be
required to elucidate the mechanisms underlying
traceraccumulation in the choroid plexus.},
cin = {INM-5},
ddc = {610},
cid = {I:(DE-Juel1)INM-5-20090406},
pnm = {5253 - Neuroimaging (POF4-525)},
pid = {G:(DE-HGF)POF4-5253},
typ = {PUB:(DE-HGF)16},
pubmed = {39826488},
UT = {WOS:001404938800001},
doi = {10.1016/j.ejmech.2025.117265},
url = {https://juser.fz-juelich.de/record/1037540},
}