Translocator Protein-18 kDa (TSPO) Positron Emission Tomography (PET) Imaging and Its Clinical Impact in Neurodegenerative Diseases

Abstract

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.

TSPO-PET and diffusion-weighted MRI for imaging a mouse model of infiltrative human glioma

“…PET or SPECT imaging targeting the translocator protein is a well-known technique for imaging of neuroinflammation as activated microglia highly express TSPO. The fact that some of the recently developed so-called second generation TSPO radioligands have already been translated and assessed in clinical studies of neurodegenerative diseases [35][36][37] , would therefor facilitate application of TSPO imaging in human gliomas.…”

TSPO PET Imaging: From Microglial Activation to Peripheral Sterile Inflammatory Diseases?

“…Limitations of TSPO PET imaging in PSIDs concern the large expression of TSPO in peripheral tissues whereas, in central nervous system, TSPO expression is low in healthy brain [39]. A body of evidence gives a M1-phenotype biomarker status of microglial TSPO expression [139].…”

Clinical trials in traumatic brain injury: cellular therapy and outcome measures

“…The degree of microglia polarization between the activated state and resting state can be determined in vivo and confirmed ex vivo. Neuroinflammation in several neurodegenerative disease processes has been evaluated in vivo with positron emission topography (PET) imaging and radioligands aimed at the 18‐kDa translocator protein (TSPO), also known as the peripheral benzodiazepine receptor (PBR) . TSPO/PBR is localized to the outer mitochondrial membrane of activated microglia/macrophages and it is significantly up regulated in response to injury and inflammation .…”