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

David R Owen; Astrid J Yeo; Roger N Gunn; Kijoung Song; Graham Wadsworth; Andrew Lewis; Chris Rhodes; David J Pulford; Idriss Bennacef; Christine A Parker; Pamela L StJean; Lon R Cardon; Vincent E Mooser; Paul M Matthews; Eugenii A Rabiner; Justin P Rubio

doi:10.1038/jcbfm.2011.147

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

David R Owen, Astrid J Yeo, Roger N Gunn, Kijoung Song, Graham Wadsworth, Andrew Lewis, Chris Rhodes, David J Pulford, Idriss Bennacef, Christine A Parker, Pamela L StJean, Lon R Cardon, Vincent E Mooser, Paul M Matthews, Eugenii A Rabiner, Justin P Rubio

Research output: Contribution to journal › Article › peer-review

611 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1-5
Number of pages	5
Journal	Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Volume	32
Issue number	1
DOIs	https://doi.org/10.1038/jcbfm.2011.147
Publication status	Published - 2012

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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. (2012). An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 32(1), 1-5. https://doi.org/10.1038/jcbfm.2011.147

@article{20c4d0ea805847f8a0d92031c704dddd,

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

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.",

author = "Owen, {David R} and Yeo, {Astrid J} and Gunn, {Roger N} and Kijoung Song and Graham Wadsworth and Andrew Lewis and Chris Rhodes and Pulford, {David J} and Idriss Bennacef and Parker, {Christine A} and StJean, {Pamela L} and Cardon, {Lon R} and Mooser, {Vincent E} and Matthews, {Paul M} and Rabiner, {Eugenii A} and Rubio, {Justin P}",

year = "2012",

doi = "10.1038/jcbfm.2011.147",

language = "English",

volume = "32",

pages = "1--5",

journal = "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism",

issn = "1559-7016",

publisher = "Nature Publishing Group",

number = "1",

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Owen, DR, Yeo, AJ, Gunn, RN, Song, K, Wadsworth, G, Lewis, A, Rhodes, C, Pulford, DJ, Bennacef, I, Parker, CA, StJean, PL, Cardon, LR, Mooser, VE, Matthews, PM, Rabiner, EA & Rubio, JP 2012, 'An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28', Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, vol. 32, no. 1, pp. 1-5. https://doi.org/10.1038/jcbfm.2011.147

An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. / Owen, David R; Yeo, Astrid J; Gunn, Roger N et al.
In: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, Vol. 32, No. 1, 2012, p. 1-5.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28

AU - Owen, David R

AU - Yeo, Astrid J

AU - Gunn, Roger N

AU - Song, Kijoung

AU - Wadsworth, Graham

AU - Lewis, Andrew

AU - Rhodes, Chris

AU - Pulford, David J

AU - Bennacef, Idriss

AU - Parker, Christine A

AU - StJean, Pamela L

AU - Cardon, Lon R

AU - Mooser, Vincent E

AU - Matthews, Paul M

AU - Rabiner, Eugenii A

AU - Rubio, Justin P

PY - 2012

Y1 - 2012

N2 - [(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.

AB - [(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.

U2 - 10.1038/jcbfm.2011.147

DO - 10.1038/jcbfm.2011.147

M3 - Article

C2 - 22008728

SN - 1559-7016

VL - 32

SP - 1

EP - 5

JO - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

IS - 1

ER -

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

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