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@ARTICLE{Willmann:889311,
author = {Willmann, Michael and Ermert, Johannes and Prante, Olaf and
Hübner, Harald and Gmeiner, Peter and Neumaier, Bernd},
title = {{R}adiosynthesis and evaluation of 18{F}-labeled dopamine
{D}4-receptor ligands},
journal = {Nuclear medicine and biology},
volume = {92},
issn = {0969-8051},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {FZJ-2021-00203},
pages = {43-52},
year = {2021},
abstract = {IntroductionThe dopamine D4 receptor (D4R) has attracted
considerable attention as potential target for the treatment
of a broad range of central nervous system disorders.
Although many efforts have been made to improve the
performance of putative radioligand candidates, there is
still a lack of D4R selective tracers suitable for in vivo
PET imaging. Thus, the objective of this work was to develop
a D4-selective PET ligand for clinical
applications.MethodsFour compounds based on previous and new
lead structures were prepared and characterized with regard
to their D4R subtype selectivity and predicted
lipophilicity. From these,
3-((4-(2-fluorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridine
I and
(S)-4-(3-fluoro-4-methoxybenzyl)-2-(phenoxymethyl)morpholine
II were selected for labeling with fluorine-18 and
subsequent evaluation by in vitro autoradiography to assess
their suitability as D4 radioligand candidates for in vivo
imaging.ResultsThe radiosynthesis of [18F]I and [18F]II was
successfully achieved by copper-mediated radiofluorination
with radiochemical yields of $7\%$ and $66\%,$ respectively.
The radioligand [18F]II showed specific binding in areas
where D4 expression is expected, whereas [18F]I did not show
any uptake in distinct brain regions and exhibited an
unacceptable degree of non-specific binding.},
cin = {INM-5},
ddc = {570},
cid = {I:(DE-Juel1)INM-5-20090406},
pnm = {525 - Decoding Brain Organization and Dysfunction
(POF4-525)},
pid = {G:(DE-HGF)POF4-525},
typ = {PUB:(DE-HGF)16},
pubmed = {32718750},
UT = {WOS:000616652500006},
doi = {10.1016/j.nucmedbio.2020.07.004},
url = {https://juser.fz-juelich.de/record/889311},
}