In vivo imaging of astrogliosis by PET

Abstract

Glial cells are non-neuronal cells that make up the central nervous system, including astrocytes, oligodendrocytes, microglia, and ependymal cells, which play an important role in brain homeostasis. However, activated microglia and reactive astrocytes cause neuroinflammation, which is closely related to neurodegeneration. Neuronal loss, gliosis, and accumulation of misfolded proteins are commonly observed in the brain of many neurodegenerative diseases at autopsy. Therefore, in vivo imaging of glial cell responses by positron emission tomography (PET) would be useful not only for understanding pathological processes, but also for differential diagnosis and evaluation of disease-modifying therapeutics targeting glial cells. The gold standard marker for reactive astrocytes is glial fibrillary acidic protein (GFAP), but no specific ligands are available. To date, there are two targets of reactive astrocytes that are under intense investigation: Monoamine oxidase-B (MAO-B) and imidazoline₂ binding site (I₂BS). PET radiopharmaceuticals for MAO-B and I₂BS have been developed and are under clinical investigation. In this chapter, we review the MAO-B and I₂BS as molecular targets for imaging reactive astrocytes and introduce the PET tracers and their clinical studies.