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

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Author(s)

Owen, DR

Yeo, AJ

Gunn, RN

Song, K

Wadsworth, G

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Type

Journal Article

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 x 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.

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Date Issued

2012

Citation

J Cereb Blood Flow Metab, 2012, 32, pp.1-5

URI

http://hdl.handle.net/10044/1/18511

DOI

https://www.dx.doi.org/10.1038/jcbfm.2011.147

ISSN

1559-7016

Publisher

NATURE PUBLISHING GROUP

Start Page

1

End Page

5

Journal / Book Title

J Cereb Blood Flow Metab

Volume

32

Issue

1

Copyright Statement

© 2012 ISCBFM All rights reserved.This work is licensed under the Creative Com-
mons Attribution-NonCommercial-No Derivative
Works 3.0 Unported License. To view a copy of this license,
visit http://creativecommons.org/licenses/by-nc-nd/3.0/

License URL

https://creativecommons.org/licenses/by-nc-nd/3.0/

Description

17/12/14 MEB. OA paper, Ok to add.

Identifier

http://www.ncbi.nlm.nih.gov/pubmed/22008728

Subjects

Acetamides/*metabolism Adult Amino Acid Substitution/genetics Binding, Competitive/genetics Blood Platelets/metabolism Cell Membrane/genetics/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/*metabolism Tritium

Publication Status

Published