Nondisplaceable Binding Is a Potential Confounding Factor in C-PBR28 Translocator Protein PET Studies.

The PET ligand C-PBR28 (-((2-(methoxy-C)-phenyl)methyl)--(6-phenoxy-3-pyridinyl)acetamide) binds to the 18-kDa translocator protein (TSPO), a biomarker of glia. In clinical studies of TSPO, the ligand total distribution volume, V, is frequently the reported outcome measure. Since V is the sum of the ligand-specific distribution volume (V) and the nondisplaceable-binding distribution volume (V), differences in V across subjects and groups will have an impact on V Here, we used a recently developed method for simultaneous estimation of V (SIME) to disentangle contributions from V and V Data from 4 previously published C-PBR28 PET studies were included: before and after a lipopolysaccharide challenge (8 subjects), in alcohol use disorder (14 patients, 15 controls), in first-episode psychosis (16 patients, 16 controls), and in Parkinson disease (16 patients, 16 controls). In each dataset, regional V estimates were obtained with a standard 2-tissue-compartment model, and brain-wide V was estimated with SIME. V was then calculated as V - V V and V were then compared across groups, within each dataset. A lower V was found for individuals with alcohol-use disorder (34%, = 0.00084) and Parkinson disease (34%, = 0.0032) than in their corresponding controls. We found no difference in V between first-episode psychosis patients and their controls, and the administration of lipopolysaccharide did not change V Our findings suggest that in TSPO PET studies, nondisplaceable binding can differ between patient groups and conditions and should therefore be considered.