Journal Article

DZNE-2025-01041

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Design, Synthesis and Preclinical Evaluation of a Brain-Permeable PET Tracer for P2Y12 Receptor Imaging in the Brain.

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

2025
ACS Washington, DC

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Please use a persistent id in citations: doi:10.1021/acs.jmedchem.5c00457

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.

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Contributing Institute(s):

1. Translational Brain Research (AG Herms)
2. Antibody Production (AG Feederle)
3. Molecular Neurodegeneration (AG Haass)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; Index Chemicus ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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