RT Journal Article SR Electronic T1 Nondisplaceable Binding Is a Potential Confounding Factor in 11C-PBR28 Translocator Protein PET Studies JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 412 OP 417 DO 10.2967/jnumed.120.243717 VO 62 IS 3 A1 Gjertrud L. Laurell A1 Pontus Plavén-Sigray A1 Aurelija Jucaite A1 Andrea Varrone A1 Kelly P. Cosgrove A1 Claus Svarer A1 Gitte M. Knudsen A1 Karolinska Schizophrenia Project Consortium A1 R. Todd Ogden A1 Francesca Zanderigo A1 Simon Cervenka A1 Ansel T. Hillmer A1 Martin Schain YR 2021 UL http://jnm.snmjournals.org/content/62/3/412.abstract AB The PET ligand 11C-PBR28 (N-((2-(methoxy-11C)-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, VT, is frequently the reported outcome measure. Since VT is the sum of the ligand-specific distribution volume (VS) and the nondisplaceable-binding distribution volume (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 4 previously published 11C-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 VT estimates were obtained with a standard 2-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 disease (34%, P = 0.0032) than in 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, nondisplaceable binding can differ between patient groups and conditions and should therefore be considered.