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000280959 1001_ $$0P:(DE-2719)9003721$$aJoseph, Emanuel$$b0$$udzne
000280959 245__ $$aDesign, Synthesis and Preclinical Evaluation of a Brain-Permeable PET Tracer for P2Y12 Receptor Imaging in the Brain.
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000280959 520__ $$aMicroglia, 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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000280959 7001_ $$0P:(DE-2719)9002311$$aKunze, Lea H$$b1$$udzne
000280959 7001_ $$aSchaefer, Rebecca$$b2
000280959 7001_ $$aPalumbo, Giovanna$$b3
000280959 7001_ $$aKugelmann, Benjamin$$b4
000280959 7001_ $$aWagner, Stephan$$b5
000280959 7001_ $$aLammich, Sven$$b6
000280959 7001_ $$0P:(DE-2719)2812867$$aFeederle, Regina$$b7$$udzne
000280959 7001_ $$aWillem, Michael$$b8
000280959 7001_ $$aWerner, Rudolf A$$b9
000280959 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b10$$udzne
000280959 7001_ $$00009-0007-4379-4436$$aLindner, Simon$$b11
000280959 773__ $$0PERI:(DE-600)1491411-6$$a10.1021/acs.jmedchem.5c00457$$gVol. 68, no. 15, p. 15543 - 15562$$n15$$p15543 - 15562$$tJournal of medicinal chemistry$$v68$$x0095-9065$$y2025
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