Nondisplaceable Binding Is a Potential Confounding Factor in 11C-PBR28 Translocator Protein PET Studies
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine |
Volume | 62 |
Issue number | 3 |
Pages (from-to) | 412-417 |
Number of pages | 6 |
ISSN | 0161-5505 |
DOIs | |
Publication status | Published - 1 Mar 2021 |
Bibliographical note
Publisher Copyright:
© 2021 by the Society of Nuclear Medicine and Molecular Imaging.
- 11C-PBR28, kinetic modeling, PET, simultaneous estimation, translocator protein
Research areas
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049343/pdf/jnm243717.pdf
Final published version
ID: 282474572