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

• Published in: The Journal of nuclear medicine (1978) Vol. 62; no. 3; pp. 412 - 417
• Main Authors: Laurell, Gjertrud L, Plavén-Sigray, Pontus, Jucaite, Aurelija, Varrone, Andrea, Cosgrove, Kelly P, Svarer, Claus, Knudsen, Gitte M, Project Consortium, Karolinska Schizophrenia, Ogden, R Todd, Zanderigo, Francesca, Cervenka, Simon, Hillmer, Ansel T, Schain, Martin
• Format: Journal Article
• Language: English
• Published: New York Society of Nuclear Medicine 01.03.2021
• Subjects: Binding; Biomarkers; Confounding (Statistics); Datasets; Disease control; Ligands; Lipopolysaccharides; Movement disorders; Neurodegenerative diseases; Parkinson's disease; Positron emission tomography; Proteins; Psychosis; Pulmonary
• ISSN: 0161-5505; 1535-5667; 1535-5667
• DOI: 10.2967/jnumed.120.243717

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.