PET Molecular Probes for Neuroinflammation in Neurodegenerative Diseases: Progress and Prospects

IF 4.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

ACS Chemical Neuroscience Pub Date : 2026-06-17 Epub Date: 2026-06-08 DOI:10.1021/acschemneuro.6c00338

Hongjun Jin*,

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引用次数: 0

Abstract

Neuroinflammation is a central pathological process underlying neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis. Positron emission tomography (PET) molecular probes now enable the noninvasive, quantitative visualization of neuroinflammatory processes in the living brain. This review surveys recent advances in PET probes targeting microglial activation markers─including the 18 kDa translocator protein (TSPO), the purinergic P2X7 receptor (P2X7R), colony-stimulating factor 1 receptor (CSF1R), and sphingosine-1-phosphate receptor 1 (S1PR1)─as well as astrocyte reactivity markers such as monoamine oxidase B (MAO-B) and imidazoline-2 binding sites (I2BS). I discuss the evolution from first-generation TSPO ligands to polymorphism-insensitive third-generation tracers, highlight emerging targets beyond TSPO, and evaluate the translational value of these probes for early diagnosis, disease staging, treatment monitoring, and drug development. Current challenges-including limited cellular specificity, genetic polymorphism effects, quantification difficulties, and clinical accessibility barriers─are analyzed alongside promising solutions. Integrating neuroinflammation PET into multimodal biomarker frameworks will be essential for advancing precision medicine in neurodegenerative diseases.

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PET分子探针用于神经退行性疾病的神经炎症：进展与展望。

神经炎症是神经退行性疾病的核心病理过程，包括阿尔茨海默病（AD）、帕金森病（PD）和肌萎缩侧索硬化症。正电子发射断层扫描（PET）分子探针现在可以对活脑中的神经炎症过程进行无创、定量的可视化。本文综述了PET探针靶向小胶质细胞激活标记物的最新进展，包括18kda转运蛋白（TSPO）、嘌呤能P2X7受体（P2X7R）、集落刺激因子1受体（CSF1R）和鞘氨醇-1-磷酸受体1 (S1PR1)，以及星形胶质细胞反应性标记物，如单胺氧化酶B （MAO-B）和咪唑啉-2结合位点（I2BS）。我讨论了从第一代TSPO配体到对多态性不敏感的第三代示踪剂的演变，强调了TSPO以外的新兴靶点，并评估了这些探针在早期诊断、疾病分期、治疗监测和药物开发方面的转化价值。当前的挑战，包括有限的细胞特异性，遗传多态性的影响，量化困难，和临床可及性障碍，分析与有希望的解决方案。将神经炎症PET整合到多模态生物标志物框架中对于推进神经退行性疾病的精准医学至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Chemical Neuroscience BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL

CiteScore

9.20

自引率

4.00%

发文量

323

审稿时长

1 months

期刊介绍： ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following: Neurotransmitters and receptors Neuropharmaceuticals and therapeutics Neural development—Plasticity, and degeneration Chemical, physical, and computational methods in neuroscience Neuronal diseases—basis, detection, and treatment Mechanism of aging, learning, memory and behavior Pain and sensory processing Neurotoxins Neuroscience-inspired bioengineering Development of methods in chemical neurobiology Neuroimaging agents and technologies Animal models for central nervous system diseases Behavioral research