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

Abstract

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 VTMethods: 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 VNDConclusion: Our findings suggest that in TSPO PET studies, nondisplaceable binding can differ between patient groups and conditions and should therefore be considered.

• Authors: Gjertrud L Laurell, Pontus Plavén-Sigray, Aurelija Jucaite, Andrea Varrone, Kelly P Cosgrove, Claus Svarer, Gitte M Knudsen, Karolinska Schizophrenia Project Consortium, R Todd Ogden, Francesca Zanderigo, Simon Cervenka, Ansel T Hillmer, Martin Schain
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 62 Issue 3 Pg. 412-417 (03 2021) ISSN: 1535-5667 [Electronic] United States
• PMID: 32680926 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by the Society of Nuclear Medicine and Molecular Imaging.

Chemical References

• (methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine
• Pyrimidines
• Receptors, GABA
• TSPO protein, human

Topics

• Artifacts
• Brain (diagnostic imaging, metabolism)
• Humans
• Positron-Emission Tomography
• Protein Binding
• Pyrimidines (metabolism)
• Receptors, GABA (metabolism)