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Joseph, E.K.* ; Kunze, L.H.* ; Schaefer, R.* ; Palumbo, G.* ; Kugelmann, B.* ; Wagner, S.* ; Lammich, S.* ; Feederle, R. ; Willem, M.* ; Werner, R.A.* ; Brendel, M.* ; Lindner, S.*

Design, synthesis and preclinical evaluation of a brain-permeable PET tracer for P2Y12 receptor imaging in the brain.

J. Med. Chem., 20 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Central-nervous-system; P2y(12) Receptor; Microglial Activation; Antagonists; Identification; Optimization; Rules
ISSN (print) / ISBN 0022-2623
e-ISSN 1520-4804
Zeitschrift Journal of Medicinal Chemistry
Quellenangaben Band: , Heft: , Seiten: 20 Artikelnummer: , Supplement: ,
Verlag American Chemical Society (ACS)
Verlagsort 1155 16th St, Nw, Washington, Dc 20036 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Monoclonal Antibodies (CF-MAB)
Förderungen Deutsche Forschungsgemeinschaft
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)