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[(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 publication

DOI

10.1038/jcbfm.2011.147

Type

Journal article

Journal

J Cereb Blood Flow Metab

Publication Date

01/2012

Volume

32

Pages

1 - 5

Keywords

Acetamides, Adult, Amino Acid Substitution, Binding, Competitive, Blood Platelets, Cell Membrane, Female, Genetic Association Studies, Humans, Isoquinolines, Male, Polymorphism, Single Nucleotide, Positron-Emission Tomography, Protein Binding, Pyridines, Radioligand Assay, Radiopharmaceuticals, Receptors, GABA, Tritium