1. Nondisplaceable Binding Is a Potential Confounding Factor in
- Author
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Gjertrud L, Laurell, Pontus, Plavén-Sigray, Aurelija, Jucaite, Andrea, Varrone, Kelly P, Cosgrove, Claus, Svarer, Gitte M, Knudsen, R Todd, Ogden, Francesca, Zanderigo, Simon, Cervenka, Ansel T, Hillmer, and Martin, Schain
- Subjects
Pyrimidines ,Receptors, GABA ,Positron-Emission Tomography ,Brain ,Humans ,Pulmonary ,Artifacts ,Protein Binding - Abstract
The PET ligand (11)C-PBR28 (N-((2-(methoxy-(11)C)-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 outcome 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 V(S). Data from 4 previously published (11)C-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.
- Published
- 2020