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Research ArticlePulmonary

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

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 and Martin Schain
Journal of Nuclear Medicine March 2021, 62 (3) 412-417; DOI: https://doi.org/10.2967/jnumed.120.243717
Gjertrud L. Laurell
1Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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Pontus Plavén-Sigray
1Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
2Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden
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Aurelija Jucaite
2Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden
3PET Science Centre, Precision Medicine and Genomics, R&D, AstraZeneca, Stockholm, Sweden
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Andrea Varrone
2Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden
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Kelly P. Cosgrove
4PET Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut
5Department of Psychiatry, Yale University, New Haven, Connecticut
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Claus Svarer
1Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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Gitte M. Knudsen
1Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
6Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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7Karolinska Schizophrenia Project Consortium, Stockholm, Sweden
R. Todd Ogden
8Department of Biostatistics, Columbia University, New York, New York
9Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, New York
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Francesca Zanderigo
8Department of Biostatistics, Columbia University, New York, New York
10Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York; and
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Simon Cervenka
2Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden
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Ansel T. Hillmer
4PET Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut
5Department of Psychiatry, Yale University, New Haven, Connecticut
11Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut
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Martin Schain
1Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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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 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.

  • PET
  • translocator protein
  • 11C-PBR28
  • simultaneous estimation
  • kinetic modeling

Footnotes

  • Published online Jul. 17, 2020.

  • © 2021 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 62 (3)
Journal of Nuclear Medicine
Vol. 62, Issue 3
March 1, 2021
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Nondisplaceable Binding Is a Potential Confounding Factor in 11C-PBR28 Translocator Protein PET Studies
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 of Nuclear Medicine Mar 2021, 62 (3) 412-417; DOI: 10.2967/jnumed.120.243717

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Nondisplaceable Binding Is a Potential Confounding Factor in 11C-PBR28 Translocator Protein PET Studies
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 of Nuclear Medicine Mar 2021, 62 (3) 412-417; DOI: 10.2967/jnumed.120.243717
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Keywords

  • PET
  • translocator protein
  • 11C-PBR28
  • simultaneous estimation
  • kinetic modeling
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