%0 Journal Article
%A Joseph, Emanuel
%A Kunze, Lea H
%A Schaefer, Rebecca
%A Palumbo, Giovanna
%A Kugelmann, Benjamin
%A Wagner, Stephan
%A Lammich, Sven
%A Feederle, Regina
%A Willem, Michael
%A Werner, Rudolf A
%A Brendel, Matthias
%A Lindner, Simon
%T Design, Synthesis and Preclinical Evaluation of a Brain-Permeable PET Tracer for P2Y12 Receptor Imaging in the Brain.
%J Journal of medicinal chemistry
%V 68
%N 15
%@ 0095-9065
%C Washington, DC
%I ACS
%M DZNE-2025-01041
%P 15543 - 15562
%D 2025
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40713021
%2 pmc:PMC12362594
%R 10.1021/acs.jmedchem.5c00457
%U https://pub.dzne.de/record/280959