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Cited by 65Medical Imaging Techniques and ApplicationsNeuroinflammation and Neurodegeneration MechanismsRadiopharmaceutical Chemistry and Applications

Kinetic modelling of [ 11 C]PBR28 for 18 kDa translocator protein PET data: A validation study of vascular modelling in the brain using XBD173 and tissue analysis

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Veronese, Mattia, Reis Marques, Tiago, Bloomfield, Peter S, Rizzo, Gaia, Singh, Nisha, Jones, Deborah, Agushi, Erjon, Mosses, Dominic +4 more·2018·Journal of Cerebral Blood Flow & Metabolism
DOI 10.1177/0271678x17712388PMC PMC6434448
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Abstract

The 18 kDa translocator protein (TSPO) is a marker of microglia activation in the central nervous system and represents the main target of radiotracers for the in vivo quantification of neuroinflammation with positron emission tomography (PET). TSPO PET is methodologically challenging given the heterogeneous distribution of TSPO in blood and brain. Our previous studies with the TSPO tracers [ 11 C]PBR28 and [ 11 C]PK11195 demonstrated that a model accounting for TSPO binding to the endothelium improves the quantification of PET data. Here, we performed a validation of the kinetic model with the additional endothelial compartment through a displacement study. Seven subjects with schizophrenia, all high-affinity binders, underwent two [ 11 C]PBR28 PET scans before and after oral administration of 90 mg of the TSPO ligand XBD173. The addition of the endothelial component provided a signal compartmentalization much more consistent with the underlying biology, as only in this model, the blocking study produced the expected reduction in the tracer concentration of the specific tissue compartment, whereas the non-displaceable compartment remained unchanged. In addition, we also studied TSPO expression in vessels using 3D reconstructions of histological data of frontal lobe and cerebellum, demonstrating that TSPO positive vessels account for 30% of the vascular volume in cortical and white matter.

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  • The endothelial component of TSPO PET, which is dependent on the vascular density in the brain, differs between regions, and may change with ageing and pathology.

    “Moreover, the endothelial component of TSPO PET, which is dependent on the vascular density in the brain, differs between regions, and may change with ageing and pathology (Mann et al., 1986; Veronese et al., 2018; Wimberley et al., 2018).”

    From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Veronese et al., 2018

  • TSPO expression in vascular endothelial cells in all blood vessels contributes to the diffuse TSPO PET signal in the healthy human brain.

    “TSPO expression in vascular endothelial cells in all blood vessels contributes to the diffuse TSPO PET signal in the healthy human brain (Veronese et al., 2018).”

    From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Veronese et al., 2018

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Authors
Veronese, M., Reis Marques, T., Bloomfield, P. S., Rizzo, G., Singh, N., Jones, D., Agushi, E., Mosses, D., Bertoldo, A., Howes, O., Roncaroli, F., & Turkheimer, F. E.
Affiliations
  • King's College London (GB)
  • Department of Psychosis Studies, IoPPN, King’s College London, London, UK
  • Imperial College London (GB)
  • University of Padua (IT)
  • Salford Royal NHS Foundation Trust (GB)
  • University of Manchester (GB)
Corresponding author
Turkheimer, Federico E
ORCID
Venue
Journal of Cerebral Blood Flow & Metabolism
Publisher
SAGE Publications
Published
2017-06-05
Volume
38
Issue
7
Pages
1227-1242
ISSN
  • 0271-678X (ISSN-L)
  • 1559-7016
DOI
10.1177/0271678x17712388
PMC
PMC6434448
OpenAlex
W2621806352
Cited by
65
References
4
Citations by year
2026: 1 · 2025: 2 · 2024: 5 · 2023: 1 · 2022: 4 · 2021: 12 · 2020: 11 · 2019: 13 · 2018: 10 · 2017: 6
FWCI
8.40
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion, other-oa)
  • Research Explorer (The University of Manchester) (submittedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (FP7/2007–2013)
  • Parkinson's UK (J-1402)
  • European Commission (2007–2013, FP7 2007-2013, FP7/2007, 278850)
  • Medical Research Council (MR/K022733/1, MR/N026934/1, MR/N026063/1)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
Keywords
[11C]PBR28, translocator protein (TSPO), kinetic modeling, vascular compartment, endothelial binding, microglial activation, neuroinflammation, schizophrenia, cerebellum, frontal lobe
MeSH terms
Acetamides, Administration, Oral, Adult, Cerebellum, Frontal Lobe, Humans, Kinetics, Male, Middle Aged, Models, Neurological, Purines, Pyridines, Radioactive Tracers, Receptors, GABA, Positron-Emission Tomography

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