Suppr超能文献

神经炎症的正电子发射断层显像(PET)成像:目前是否有比转运蛋白18 kDa(TSPO)更可靠的替代物?

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

作者信息

Chauveau Fabien, Winkeler Alexandra, Chalon Sylvie, Boutin Hervé, Becker Guillaume

机构信息

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.

Université Paris-Saclay, Inserm, CNRS, CEA, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du général Leclerc, 91401, Orsay, France.

出版信息

Mol Psychiatry. 2025 Jan;30(1):213-228. doi: 10.1038/s41380-024-02656-9. Epub 2024 Jul 13.

Abstract

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.

摘要

在过去几十年中,神经炎症在神经精神疾病中的作用引起了人们呈指数级增长的兴趣。这一趋势的一个关键驱动因素是能够使用靶向转运蛋白18 kDa(TSPO)的正电子发射断层扫描(PET)放射性配体在体内对脑炎症进行成像,已知TSPO在炎症事件发生时在活化的小胶质细胞和星形胶质细胞中表达,并且在内皮细胞中持续表达。TSPO是一种线粒体蛋白,主要在活化时由小胶质细胞表达,但在某些情况下也由星形胶质细胞表达,在内皮细胞中持续表达。因此,我们目前对神经炎症动态的理解因缺乏可用于PET成像的替代靶点而受到阻碍。我们对除TSPO之外用于神经炎症PET成像的放射性示踪剂进行了系统的搜索和综述。通过文献筛选(包括以前的叙述性综述)确定了以下感兴趣的靶点:P2Y12R、P2X7R、CSF1R、COX(小胶质细胞靶点)、MAO-B、I2BS(星形胶质细胞靶点)、CB2R和S1PRs(不是单一细胞类型所特有的)。我们确定了每个靶点的开发水平并提供了范围综述。引人注目的是,星形胶质细胞生物标志物MAO-B在临床研究中进展最远,而很少有放射性示踪剂(特别是靶向S1P1R、CSF1R的)正在临床研究中实施。其他靶点,如CB2R和P2X7R,在临床研究中已被证明令人失望(例如信号差、疾病状态下无变化等)。虽然星形胶质细胞靶点很有前景,但开发针对小胶质细胞活化的新生物标志物和示踪剂已被证明具有挑战性。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验