An 18-kDa Translocator Protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28
2012
[11C]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
affinityof 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
affinityphenotype (P value=3.1 × 10−13). The TSPO Ala147Thr polymorphism predicts PBR28 binding
affinityin human platelets. As all second-generation TSPO PET
radioligandstested hitherto display a trimodal distribution in binding
affinityanalogous to PBR28, testing for this polymorphism may allow quantitative interpretation of TSPO PET studies with these
radioligands.
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