Imaging brain microglial activation using positron emission tomography and translocator protein-specific radioligands

Microglia are rapidly activated by a wide range of neuropathological insults. Quantifying microglial density in vivo would allow a new, potentially important range of clinic-pathological correlations. Microglia express the 18kDa translocator protein (TSPO) which can be quantified by the positron emission tomography (PET) ligand [(11)C]PK11195, although signal quantification is limited by nonspecific binding. New generation TSPO radioligands with an improved signal-to-noise ratio are now available, but variation in their binding affinity for the TSPO between subjects complicates their use. This review describes the principles of PET imaging, the rationale and challenges in targeting the TSPO as means of quantifying microglial activation in vivo, and disease applications that have been studied with TSPO-PET hitherto.