There is increasing evidence showing the heterogeneity of microglia activation in neuroinflammatory and neurodegenerative diseases. It has been hypothesized that pro-inflammatory microglia are detrimental and contribute to disease progression, while anti-inflammatory microglia play a role in damage repair and remission. The development of therapeutics targeting the deleterious glial activity and modulating it into a regenerative phenotype relies heavily upon a clearer understanding of the microglia dynamics during disease progression and the ability to monitor therapeutic outcome in vivo. To that end, molecular imaging techniques are required to assess microglia dynamics and study their role in disease progression as well as to evaluate the outcome of therapeutic interventions. Positron emission tomography (PET) is such a molecular imaging technique, and provides unique capabilities for non-invasive quantification of neuroinflammation and has the potential to discriminate between microglia phenotypes and define their role in the disease process. However, several obstacles limit the possibility for selective in vivo imaging of microglia phenotypes mainly related to the poor characterization of specific targets that distinguish the two ends of the microglia activation spectrum and lack of suitable tracers. PET tracers targeting translocator protein 18 kDa (TSPO) have been extensively explored, but despite the success in evaluating neuroinflammation they failed to discriminate between microglia activation statuses. In this review, we highlight the current knowledge on the microglia phenotypes in the major neuroinflammatory and neurodegenerative diseases. We also discuss the current and emerging PET imaging targets, the tracers and their potential in discriminating between the pro- and anti-inflammatory microglia activation states.

中文翻译：

---

小胶质细胞动态表型的 PET 成像

越来越多的证据表明神经炎症和神经退行性疾病中小胶质细胞活化的异质性。据推测，促炎小胶质细胞是有害的并有助于疾病进展，而抗炎小胶质细胞在损伤修复和缓解中发挥作用。针对有害神经胶质活性并将其调节为再生表型的治疗方法的开发在很大程度上依赖于对疾病进展过程中小胶质细胞动力学的更清晰理解以及在体内监测治疗结果的能力. 为此，需要分子成像技术来评估小胶质细胞动力学并研究它们在疾病进展中的作用以及评估治疗干预的结果。正电子发射断层扫描 (PET) 就是这样一种分子成像技术，它为神经炎症的非侵入性量化提供了独特的能力，并有可能区分小胶质细胞表型并确定它们在疾病过程中的作用。然而，一些障碍限制了体内选择性的可能性小胶质细胞表型的成像主要与区分小胶质细胞激活谱两端的特定目标的表征不佳和缺乏合适的示踪剂有关。已经广泛探索了靶向转运蛋白 18 kDa (TSPO) 的 PET 示踪剂，但尽管在评估神经炎症方面取得了成功，但它们未能区分小胶质细胞的激活状态。在这篇综述中，我们重点介绍了当前对主要神经炎症和神经退行性疾病中小胶质细胞表型的了解。我们还讨论了当前和新兴的 PET 成像目标、示踪剂及其在区分促炎和抗炎小胶质细胞激活状态方面的潜力。