Non-displaceable binding is a potential confounding factor in ¹¹CPBR28 TSPO PET studies

Abstract

The positron emission tomography (PET) ligand ¹¹C-PBR28 binds to the 18kDa translocator protein (TSPO), a biomarker of glia. In clinical studies of TSPO, the ligand total distribution volume, VT, is frequently the reported outcome measure. Since VT is the sum of the ligand specific (VS) and non-displaceable binding (VND), differences in VND across subjects and groups will have an impact on VT. Methods: Here, we used a recently developed method for simultaneous estimation of VND (SIME) to disentangle contributions from VND and VS. Data from four previously published ¹¹C-PBR28 PET studies were included: (i) before and after a lipopolysaccharide challenge (8 subjects), (ii) in alcohol use disorder (14 patients, 15 controls), (iii) in first-episode psychosis (16 patients, 16 controls), and (iv) in Parkinson’s disease (16 patients, 16 controls). In each dataset, regional VT estimates were obtained with a standard two-tissue compartment model, and brain-wide VND was estimated with SIME. VS was then calculated as VT–VND. VND and VS were then compared across groups, within each dataset. Results: A lower VND was found for individuals with alcohol use disorder (34%, P = 0.00084) and Parkinson’s disease (34%, P = 0.0032), when compared to their corresponding controls. We found no difference in VND between first-episode psychosis patients and their controls, and the administration of lipopolysaccharide did not change VND. Conclusion: Our findings suggest that in TSPO PET studies, non-displaceable binding can differ between patient groups and conditions and should therefore be taken into account.