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

The PET ligand C-11-PBR28 (N-((2-(methoxy-C-11)-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 out come 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 VS. Data from 4 previously published C-11-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.

Automated summary

The study utilized a novel method SIME to estimate V-ND, demonstrating significantly lower V-ND in patients with alcohol use disorder and Parkinson's disease compared to controls. The findings suggest that differences in nondisplaceable binding may exist between different patient groups and conditions in TSPO PET studies.