PET imaging of neuroinflammation: any credible alternatives to TSPO yet?

Autor: Chauveau F; Université Claude Bernard Lyon 1, Centre de Recherche en Neurosciences de Lyon, Inserm U1028, CNRS UMR5292, BIORAN, Groupement Hospitalier Est - CERMEP, 59 boulevard Pinel, 69677, Bron, Cedex, France., Winkeler A; Université Paris-Saclay, Inserm, CNRS, CEA, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du général Leclerc, 91401, Orsay, France., Chalon S; UMR 1253 iBrain, Université de Tours - INSERM, Bâtiment Planiol, UFR de Médecine, 10 Boulevard Tonnellé, 37032, Tours, Cedex 01, France., Boutin H; UMR 1253 iBrain, Université de Tours - INSERM, Bâtiment Planiol, UFR de Médecine, 10 Boulevard Tonnellé, 37032, Tours, Cedex 01, France. herve.boutin@inserm.fr., Becker G; Université Claude Bernard Lyon 1, Centre de Recherche en Neurosciences de Lyon, Inserm U1028, CNRS UMR5292, BIORAN, Groupement Hospitalier Est - CERMEP, 59 boulevard Pinel, 69677, Bron, Cedex, France.; Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail, 14 rue Pierre et Marie Curie, 94701, Maisons-Alfort, Cedex, France.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2025 Jan; Vol. 30 (1), pp. 213-228. Date of Electronic Publication: 2024 Jul 13.
DOI: 10.1038/s41380-024-02656-9
Abstrakt: Over the last decades, the role of neuroinflammation in neuropsychiatric conditions has attracted an exponentially growing interest. A key driver for this trend was the ability to image brain inflammation in vivo using PET radioligands targeting the Translocator Protein 18 kDa (TSPO), which is known to be expressed in activated microglia and astrocytes upon inflammatory events as well as constitutively in endothelial cells. TSPO is a mitochondrial protein that is expressed mostly by microglial cells upon activation but is also expressed by astrocytes in some conditions and constitutively by endothelial cells. Therefore, our current understanding of neuroinflammation dynamics is hampered by the lack of alternative targets available for PET imaging. We performed a systematic search and review on radiotracers developed for neuroinflammation PET imaging apart from TSPO. The following targets of interest were identified through literature screening (including previous narrative reviews): P2Y12R, P2X7R, CSF1R, COX (microglial targets), MAO-B, I2BS (astrocytic targets), CB2R & S1PRs (not specific of a single cell type). We determined the level of development and provided a scoping review for each target. Strikingly, astrocytic biomarker MAO-B has progressed in clinical investigations the furthest, while few radiotracers (notably targeting S1P1Rs, CSF1R) are being implemented in clinical investigations. Other targets such as CB2R and P2X7R have proven disappointing in clinical studies (e.g. poor signal, lack of changes in disease conditions, etc.). While astrocytic targets are promising, development of new biomarkers and tracers specific for microglial activation has proven challenging.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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