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

被引：606

作者：

Owen, David R. ^{[1
,2
]}

Yeo, Astrid J. ^{[3
,4
,5
]}

Gunn, Roger N. ^{[2
,6
,7
]}

Song, Kijoung ^{[3
,4
,5
]}

Wadsworth, Graham ^{[2
]}

Lewis, Andrew ^{[1
]}

Rhodes, Chris ^{[1
]}

Pulford, David J. ^{[4
,5
]}

Bennacef, Idriss ^{[2
]}

Parker, Christine A. ^{[2
,6
]}

StJean, Pamela L. ^{[3
,4
,5
]}

Cardon, Lon R. ^{[3
,4
,5
]}

Mooser, Vincent E. ^{[3
,4
,5
]}

Matthews, Paul M. ^{[2
,6
]}

Rabiner, Eugenii A. ^{[2
,6
]}

Rubio, Justin P. ^{[3
,4
,5
]}

机构：

[1] Hammersmith Hosp, Imperial Coll London, Div Expt Med, Dept Med, London W12 0NN, England

[2] Hammersmith Hosp, GlaxoSmithKline Res & Dev, Clin Imaging Ctr, London W12 0NN, England

[3] GlaxoSmithKline Res & Dev Ltd, Genet, Stevenage, Herts, England

[4] GlaxoSmithKline Res & Dev Ltd, Genet, King Of Prussia, PA USA

[5] GlaxoSmithKline Res & Dev Ltd, Genet, Res Triangle Pk, NC USA

[6] Hammersmith Hosp, Imperial Coll London, Ctr Neurosci, Dept Med, London W12 0NN, England

[7] Univ Oxford, Dept Engn Sci, Oxford OX1 3PJ, England

来源：

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2012年 / 32卷 / 01期

关键词：

Ala147Thr; PBR28; polymorphism; radioligand binding; TSPO; 18; KDA; NEUROINFLAMMATION; MICROGLIA; BRAIN;

D O I：

10.1038/jcbfm.2011.147

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

[(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 =3.1x10(-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. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1-5; doi:10.1038/jcbfm.2011.147; published online 19 October 2011

引用

页码：1 / 5

页数：5

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