An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28.

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Serval ID
serval:BIB_406D1DEA8A50
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Production externe
Title
An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28.
Journal
Journal of Cerebral Blood Flow and Metabolism
Author(s)
Owen D.R., Yeo A.J., Gunn R.N., Song K., Wadsworth G., Lewis A., Rhodes C., Pulford D.J., Bennacef I., Parker C.A., StJean P.L., Cardon L.R., Mooser V.E., Matthews P.M., Rabiner E.A., Rubio J.P.
ISSN
1559-7016 (Electronic)
ISSN-L
0271-678X
Publication state
Published
Issued date
2012
Volume
32
Number
1
Pages
1-5
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
[(11)C]PBR28 binds the 18-kDa Translocator Protein (TSPO) and is used in positron emission tomography (PET) to detect microglial activation. However, quantitative interpretations of signal are confounded by large interindividual variability in binding affinity, which displays a trimodal distribution compatible with a codominant genetic trait. Here, we tested directly for an underlying genetic mechanism to explain this. Binding affinity of PBR28 was measured in platelets isolated from 41 human subjects and tested for association with polymorphisms in TSPO and genes encoding other proteins in the TSPO complex. Complete agreement was observed between the TSPO Ala147Thr genotype and PBR28 binding affinity phenotype (P value=3.1 × 10(-13)). The TSPO Ala147Thr polymorphism predicts PBR28 binding affinity in human platelets. As all second-generation TSPO PET radioligands tested hitherto display a trimodal distribution in binding affinity analogous to PBR28, testing for this polymorphism may allow quantitative interpretation of TSPO PET studies with these radioligands.
Keywords
Acetamides/metabolism, Adult, Amino Acid Substitution/genetics, Binding, Competitive/genetics, Blood Platelets/metabolism, Cell Membrane/genetics, Cell Membrane/metabolism, Female, Genetic Association Studies, Humans, Isoquinolines/metabolism, Male, Polymorphism, Single Nucleotide, Positron-Emission Tomography, Protein Binding, Pyridines/metabolism, Radioligand Assay, Radiopharmaceuticals/metabolism, Receptors, GABA/genetics, Receptors, GABA/metabolism, Tritium
DOI
10.1038/jcbfm.2011.147
Pubmed
22008728
Web of science
000299010000002
Open Access
Yes
Create date
22/03/2012 10:44
Last modification date
20/08/2019 14:38
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