Contributors: Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Radiopharmaceutical and Neurochemical Biomarkers (BIORAN); Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL); LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS); Service Hospitalier Frédéric Joliot (SHFJ); Université Paris-Saclay-Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Imaging, Brain & Neuropsychiatry (iBraiN); Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM); Laboratoire de Lyon ANSES; Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES); ANR-11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011); ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011); ANR-21-CE18-0067,PURImaging,PURImaging – Développement de radioligands ciblant le récepteur PURInergique P2Y12, une cible prometteuse pour l'imagerie tomographie par émission de positons (TEP) de la neuroinflammation(2021); ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011)
نبذة مختصرة : This is a preprint version of the manuscript published by Springer Nature in Molecular Psychiatry. Link to full published version: https://www.nature.com/articles/s41380-024-02656-9 or https://doi.org/10.1038/s41380-024-02656-9 ; International audience ; 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.
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