Translocator Protein-18 kDa (TSPO) Positron Emission Tomography (PET) Imaging and Its Clinical Impact in Neurodegenerative Diseases.
Translocator Protein-18 kDa (TSPO) Positron Emission Tomography (PET) Imaging and Its Clinical Impact in Neurodegenerative Diseases.
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DOI：
10.3390/ijms18040785
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发表时间：
2017-04-07
影响因子：
5.6
通讯作者：
Arlicot N
中科院分区：
文献类型：
--
作者：
Dupont AC;Largeau B;Santiago Ribeiro MJ;Guilloteau D;Tronel C;Arlicot N
在神经退行性疾病中激活的小胶质细胞的体内探索可通过正电子发射断层扫描（PET）成像实现，使用靶向转运蛋白-18 kDa（TSPO）的专用放射性药物。在这篇综述中，我们强调了在过去20年中取得的重大进展，感谢TSPO PET成像，以确定小胶质细胞激活和神经炎症在神经退行性疾病，包括帕金森病，亨廷顿病，痴呆症，肌萎缩侧索硬化症，多发性硬化症，以及精神疾病的病理生理意义。TSPO作为人脑中活化的小胶质细胞的分子生物标志物的程度和上调现在在这些病理学中被广泛记录，但其意义，特别是其关于疾病阶段的保护或有害作用，仍然存在争议。因此，我们揭示了新的和合理的建议，以提高TSPO PET成像的生物医学研究的贡献，通过探索小胶质细胞的作用和与脑实质中的其他细胞的相互作用。考虑了将TSPO PET放射性药物与其他生物标志物（细胞代谢、神经传递或异常蛋白质聚集体的PET成像，以及其他成像方式和外周细胞因子水平测量和/或代谢组学分析）相关联的多重方法。最后，将TSPO PET成像作为神经炎症的常规生物标志物的实际临床影响纳入当前神经退行性疾病诊断和治疗策略的发展中。
In vivo exploration of activated microglia in neurodegenerative diseases is achievable by Positron Emission Tomography (PET) imaging, using dedicated radiopharmaceuticals targeting the translocator protein-18 kDa (TSPO). In this review, we emphasized the major advances made over the last 20 years, thanks to TSPO PET imaging, to define the pathophysiological implication of microglia activation and neuroinflammation in neurodegenerative diseases, including Parkinson’s disease, Huntington’s disease, dementia, amyotrophic lateral sclerosis, multiple sclerosis, and also in psychiatric disorders. The extent and upregulation of TSPO as a molecular biomarker of activated microglia in the human brain is now widely documented in these pathologies, but its significance, and especially its protective or deleterious action regarding the disease’s stage, remains under debate. Thus, we exposed new and plausible suggestions to enhance the contribution of TSPO PET imaging for biomedical research by exploring microglia’s role and interactions with other cells in brain parenchyma. Multiplex approaches, associating TSPO PET radiopharmaceuticals with other biomarkers (PET imaging of cellular metabolism, neurotransmission or abnormal protein aggregates, but also other imaging modalities, and peripheral cytokine levels measurement and/or metabolomics analysis) was considered. Finally, the actual clinical impact of TSPO PET imaging as a routine biomarker of neuroinflammation was put into perspective regarding the current development of diagnostic and therapeutic strategies for neurodegenerative diseases.