Microglial Positron Emission Tomography Imaging In Vivo : Positron Emission Tomography Radioligands: Utility in Research and Clinical Practice.

ABSTRACT

Microglia, the resident immune cells of the central nervous system (CNS) play a key role in regulating and maintaining homeostasis in the brain. However, the CNS is also vulnerable to infections and inflammatory processes. In response to CNS perturbations, microglia become reactive, notably with expression of the translocator protein (TSPO), primarily on their outer mitochondrial membrane. Despite TSPO being commonly used as a marker for microglia, it is also present in other cell types such as astrocytes. Positron emission tomography (PET) ligands that target the TSPO enable the noninvasive detection and quantification of glial reactivity. While some limitations were raised, TSPO PET remains an attractive biomarker of CNS infection and inflammation. This book chapter delves into the development and application of microglial PET imaging with a focus on the TSPO PET. First, we provide an overview of the evolution of TSPO PET radioligands from first-generation to second-generation ligands and their applications in studying neuroinflammation (or CNS inflammation). Subsequently, we discuss the limitations and challenges associated with TSPO PET. Then we go on to explore non-TSPO targets for microglial PET imaging. Finally, we conclude with future directions for research and clinical practice in this field.