Translocator Protein (18 kDa) Polymorphism (rs6971) Explains in-vivo Brain Binding Affinity of the PET Radioligand [ 18 F]-FEPPA
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[(18)F]-FEPPA binds to the 18-kDa translocator protein (TSPO) and is used in positron emission tomography (PET) to detect microglial activation. However, quantitative interpretations of the PET signal with new generation TSPO PET radioligands are confounded by large interindividual variability in binding affinity. This presents as a trimodal distribution, reflecting high-affinity binders (HABs), low-affinity binder (LAB), and mixed-affinity binders (MABs). Here, we show that one polymorphism (rs6971) located in exon 4 of the TSPO gene, which results in a nonconservative amino-acid substitution from alanine to threonine (Ala147Thr) in the TSPO protein, predicts [(18)F]-FEPPA total distribution volume in human brains. In addition, [(18)F]-FEPPA exhibits clearly different features in the shape of the time activity curves between genetic groups. Testing for the rs6971 polymorphism may allow quantitative interpretation of TSPO PET studies with new generation of TSPO PET radioligands.
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Clinical use of second-generation TSPO tracers is complicated by a single nucleotide polymorphism in the Tspo gene that alters binding affinity in a proportion of humans.
“However, the clinical use of these second-generation tracers is complicated by a single nucleotide polymorphism in the Tspo gene that alters its binding affinity in a proportion of humans.”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [20]
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- Authors
- Mizrahi, R., Rusjan, P. M., Kennedy, J., Pollock, B., Mulsant, B., Suridjan, I., De Luca, V., Wilson, A. A., & Houle, S.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- University of Toronto (CA)
- Department of Psychiatry, University of Toronto, Ontario, Canada
- Corresponding author
- Mizrahi, Romina
- ORCID
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2012-04-04
- Volume
- 32
- Issue
- 6
- Pages
- 968-972
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC3367231
- OpenAlex
- W2070082204
- Cited by
- 155
- References
- 22
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 6 · 2023: 10 · 2022: 8 · 2021: 17 · 2020: 14 · 2019: 10 · 2018: 16 · 2017: 14 · 2016: 9 · 2015: 12 · 2014: 16 · 2013: 4 · 2012: 3
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Keywords
- translocator protein (TSPO), [18F]FEPPA, microglial activation, volume of distribution, time-activity curves, interindividual variability
- MeSH terms
- Adult, Aged, Anilides, Exons, Female, Humans, Male, Middle Aged, Polymorphism, Genetic, Protein Binding, Pyridines, Radiography, Microglia, Receptors, GABA, Amino Acid Substitution, Positron-Emission Tomography
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