TSPO PET Imaging as a Biomarker of Neuroinflammation in Neurodegenerative Disorders

Neuroinflammation is a hallmark feature across the spectrum of neurodegenerative disorders. Central to neuroinflammation is the activation of microglia and astrocytes. Activated microglia, and perhaps astrocytes, display an upregulation of TSPO in neuroinflammation and in neurodegenerative disease models, based on culture and animal studies. This indicates TSPO may be a biomarker for neuroinflammation, however, clinical use of TSPO-targeting positron emission tomography to monitor neuroinflammation in neurodegenerative disorders has been hindered by the presence of a TSPO polymorphism (A147T). TSPO ligands bind with lower affinity to A147T TSPO, restricting the clinical utility of this approach. This chapter reviews the ongoing efforts to produce ligands that bind highly to A147T TSPO. It also explores the question of how to interpret the TSPO PET signal, by examining which microglial phenotypes upregulate TSPO in neuroinflammation, and what other brain cell types might contribute to the TSPO PET signal.