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

Détails

ID Serval
serval:BIB_406D1DEA8A50
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28.
Périodique
Journal of Cerebral Blood Flow and Metabolism
Auteur(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
Statut éditorial
Publié
Date de publication
2012
Volume
32
Numéro
1
Pages
1-5
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
[(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.
Mots-clé
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
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/03/2012 10:44
Dernière modification de la notice
08/05/2019 17:37
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