Impact of Endothelial 18-kDa Translocator Protein on the Quantification of18F-DPA-714
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18F-DPA-714 is a second-generation tracer for PET imaging of the 18-kDa translocator protein (TSPO), a marker of neuroinflammation. Analysis and interpretation of TSPO PET are challenging, especially because of the basal expression of TSPO. The aim of this study was to evaluate a compartmental model that accounts for the effect of endothelial TSPO binding on the quantification of 18F-DPA-714 PET scans from a cohort of healthy subjects. Methods: Fifteen healthy subjects (9 high-affinity binders and 6 mixed-affinity binders) underwent 18F-DPA-714 PET scans with arterial blood sampling and metabolite analysis. The kinetic parameters were quantified using a 2-tissue compartmental model (2TC) as well as a 2TC with an extra, irreversible, compartment for endothelial binding (2TC-1K). These regional parameters and messenger RNA (mRNA) expression specific to endothelial cells were correlated with regional TSPO mRNA expression. Results: The 2TC-1K model was more appropriate than the 2TC for 81% of fits. The total volume of distribution was significantly reduced by 21% ± 12% across all regions with the 2TC-1K, compared with the 2TC. The endothelial binding parameter Kb varied highly across brain regions. Kb strongly and significantly correlated with all 3 probes extracted for TSPO mRNA expression (r = 0.80, r = 0.79, and r = 0.90), but no correlation was seen with the other binding parameters from the 2TC-1K. For the 2TC, there was a lower but significant correlation between the volume of distribution and one of the TSPO mRNA probes (r = 0.65). A strong, significant correlation was seen between mRNA for TSPO and genes specific to endothelial cells. Conclusion: Accounting for endothelial TSPO in the kinetic model improved the fit of PET data. The high correlation between Kb and TSPO mRNA suggests that the 2TC-1K model reveals more biologic information about the regional density of TSPO than the 2TC. The correlation between TSPO and endothelial cell mRNA supports the relationship between the regional variation of Kb and endothelial TSPO. These results can improve the estimation of binding parameter estimates from 18F-DPA-714 PET, especially in diseases that induce vascular change.
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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 Wimberley et al., 2018
The Kinetic Parameters section reports that endothelial binding varied across brain regions, and the Discussion cautions that vascular degeneration, angiogenesis, or inflammation in disease could affect PET interpretation (page numbers not supplied). The paper does not establish that the PET component depends on brain vascular density or report changes with ageing; its PET cohort comprised healthy subjects. (LLM, conf=0.85)
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Imaging Glutamatergic and GABAergic Abnormalities in Mood Disorders
Scotti-Muzzi, E., Otaduy, M. C. G., Soeiro‐de‐Souza, M. G., & Machado‐Vieira, R. (2021) · Cambridge University Press eBooks · doi:10.1017/9781108623018.010
Molecular Imaging of Dopamine and Antipsychotics in Bipolar Disorder
Jauhar, S. (2021) · Cambridge University Press eBooks · doi:10.1017/9781108623018.019
Magnetoencephalography Studies in Mood Disorders
Nugent, A. C. (2021) · Cambridge University Press eBooks · doi:10.1017/9781108623018.016
Selvaraj, S., Brambilla, P., & Soares, J. C. (2021) · Cambridge University Press eBooks · doi:10.1017/9781108623018.022
Selvaraj, S., Brambilla, P., & Soares, J. C. (2021) · Cambridge University Press eBooks · doi:10.1017/9781108623018.001
- Authors
- Wimberley, C., Lavisse, S., Brulon, V., Peyronneau, M.-A., Leroy, C., Bodini, B., Remy, P., Stankoff, B., Buvat, I., & Bottlaender, M.
- Affiliations
- Université Paris-Sud (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2017-08-03
- Volume
- 59
- Issue
- 2
- Pages
- 307-314
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- OpenAlex
- W2742902344
- Semantic Scholar
- a703af66aa6396ba676cf958204e76c09a92d77d
- Cited by
- 63
- References
- 32
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 4 · 2022: 1 · 2021: 33 · 2020: 4 · 2019: 7 · 2018: 7 · 2017: 1
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-08-MNPS-0016, ANR-17-EURE-0017, ANR-11-INBS-0006, ANR-11-INBS-0011)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Keywords
- [18F]DPA-714, translocator protein (TSPO), TSPO, PET quantification, compartmental kinetic model, neuroinflammation imaging, brain health, volume of distribution, arterial blood sampling, metabolite analysis
- MeSH terms
- Brain, Female, Fluorine Radioisotopes, Gene Expression Regulation, Humans, Image Processing, Computer-Assisted, Kinetics, Male, Middle Aged, Pyrazoles, Pyrimidines, Receptors, GABA, Endothelial Cells, Positron-Emission Tomography, Signal-To-Noise Ratio
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