The role of TSPO PET in assessing neuroinflammation

Neuroinflammation is associated with increased expression of the 18-kDa translocator protein (TSPO), also known as the peripheral benzodiazepine receptor (PBR), which is present on the mitochondria of activated microglia, astroglia and macrophages. TSPO positron emission tomography (PET) ligands have been used in neuroinflammation research for over 20 years. The first-generation tracer 11 C-PK11195 has some limitations including low signal-to-noise ratio making more subtle neuroinflammation difficult to detect in brain tissue. More recently, second- and third-generation TSPO-specific radiotracers have been developed to overcome these hurdles and have proven useful in assessment of neuroinflammation in a variety of neurological and psychiatric conditions. However, one drawback of the newer ligands is the need to genotype for rs6971 polymorphisms prior to imaging. The polymorphism determines radiotracer uptake since low-affinity binders (Thr/Thr) have to be excluded, and statistical analyses require adjustments depending on whether participants are mixed (Ala/Thr) or high affinity (Ala/Ala) binders.