The development of PET radioligands for imaging the translocator protein (18 kDa): What have we learned?

The translocator protein (TSPO; 18 kDa), formerly known as the peripheral benzodiazepine receptor (PBR), is minimally expressed in the healthy brain. On the other hand, increased levels of TSPO have been noted in brain disorders for which an immune response is elicited. This increase in TSPO expression has been reported to coincide with the process of microglial activation making the measurement of TSPO density a useful indicator of active brain disease. To this end several new classes of TSPO positron emission tomography radioligands have been developed and evaluated. However, the incomplete pharmacological characterization of the TSPO and its ligands as well as differences in pathophysiology, pharmacology and molecular nature across species and tissue types means that caution must be exercised when comparing data obtained with various TSPO radioligands. A re‐evaluation of our interpretation of imaging data, which better correlates with our current understanding of TSPO pharmacology in disease, requires consideration.