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The PET ligand 11 C-PBR28 ( N -((2-(methoxy- 11 C)-phenyl)methyl)- N -(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 T , is frequently the reported outcome measure. Since V T is the sum of the ligand-specific distribution volume (V S ) and the nondisplaceable-binding distribution volume (V ND ), differences in V ND across subjects and groups will have an impact on V T  Methods: Here, we used a recently developed method for simultaneous estimation of V ND (SIME) to disentangle contributions from V ND and V S Data from 4 previously published 11 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 T estimates were obtained with a standard 2-tissue-compartment model, and brain-wide V ND was estimated with SIME. V S was then calculated as V T - V ND V ND and V S were then compared across groups, within each dataset. Results: A lower V ND was found for individuals with alcohol-use disorder (34%, P = 0.00084) and Parkinson disease (34%, P = 0.0032) than in their corresponding controls. We found no difference in V ND between first-episode psychosis patients and their controls, and the administration of lipopolysaccharide did not change V ND  Conclusion: Our findings suggest that in TSPO PET studies, nondisplaceable binding can differ between patient groups and conditions and should therefore be considered.

Nondisplaceable Binding Is a Potential Confounding Factor in 11C-PBR28 Translocator Protein PET Studies

Nondisplaceable Binding Is a Potential Confounding Factor in ¹¹C-PBR28 Translocator Protein PET Studies