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@ARTICLE{Joseph:280959,
author = {Joseph, Emanuel and Kunze, Lea H and Schaefer, Rebecca and
Palumbo, Giovanna and Kugelmann, Benjamin and Wagner,
Stephan and Lammich, Sven and Feederle, Regina and Willem,
Michael and Werner, Rudolf A and Brendel, Matthias and
Lindner, Simon},
title = {{D}esign, {S}ynthesis and {P}reclinical {E}valuation of a
{B}rain-{P}ermeable {PET} {T}racer for {P}2{Y}12 {R}eceptor
{I}maging in the {B}rain.},
journal = {Journal of medicinal chemistry},
volume = {68},
number = {15},
issn = {0095-9065},
address = {Washington, DC},
publisher = {ACS},
reportid = {DZNE-2025-01041},
pages = {15543 - 15562},
year = {2025},
abstract = {Microglia, the innate immune cells of the central nervous
system (CNS), act as first responders to brain injury. Their
ability to switch between different neuroprotective and
neurotoxic phenotypes, plays a central role in maintaining
brain homeostasis. Recently, the P2Y12 receptor (P2Y12R) has
been identified as a promising molecular biomarker for
microglia activity, as its expression level is dependent on
microglia phenotype and function. P2Y12R positron emission
tomography (PET) might be a valuable diagnostic tool,
however, tracers with sufficient brain retention have not
been reported so far. Herein, we report a brain-permeable
P2Y12R PET tracer for in vivo imaging of P2Y12R-positive
microglia. Nicotinate [18F]12 exhibited nanomolar affinity
and specificity for the target receptor and showed a reduced
uptake in microglia-depleted (PLX) mice, in comparison to WT
and Trem2 knockout (Trem2-/-) mice. Ex vivo
immunohistochemistry (IHC) and PET data revealed a strong
correlation between microglia abundance, P2Y12R expression
levels and tracer uptake.},
cin = {AG Herms / AG Feederle / AG Haass},
ddc = {610},
cid = {I:(DE-2719)1110001 / I:(DE-2719)1140004 /
I:(DE-2719)1110007},
pnm = {352 - Disease Mechanisms (POF4-352) / 899 - ohne Topic
(POF4-899)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40713021},
pmc = {pmc:PMC12362594},
doi = {10.1021/acs.jmedchem.5c00457},
url = {https://pub.dzne.de/record/280959},
}