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The impact of the rs6971 polymorphism in TSPO for quantification and study design

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Abstract

Second-generation translocator protein (TSPO) radioligands were developed to circumvent the technical short comings of 11C-PK11195, the first TSPO targeting tracer. However, in early clinical positron emission tomography (PET) studies they displayed greater inter- and intra-subject variability than was expected given the promising characteristics they showed in preclinical and in vitro studies. A great deal of this variability, although not all, can be explained by the rs6971 polymorphism in the gene encoding TSPO. This polymorphism causes a single amino acid substitution in the TSPO which, for all second-generation tracers tested in man hitherto, reduces binding affinity in mutants relative to wild type. This has obvious implications for interpretation of data, because inter-subject comparisons in PET studies are predicated on the assumption that binding affinity is consistent across all subjects. In this paper, we discuss the implications of the rs6971 polymorphism on study design, analysis and interpretation of data for clinical PET studies using second-generation TSPO radioligands.

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Authors and Affiliations

  1. Division of Brain Sciences, Department of Medicine, Imperial College, 5th Floor, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK

    D. R. Owen & R. N. Gunn

  2. Abbvie, Integrated Sciences and Technology, 1 North Waukegan Rd, North Chicago, USA

    Q. Guo

  3. Imanova, Centre for Imaging Sciences, London, UK

    E. A. Rabiner & R. N. Gunn

  4. Centre for Neuroimaging Sciences, Institute of Psychiatry, King’s College London, London, UK

    E. A. Rabiner

Authors
  1. D. R. Owen
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  2. Q. Guo
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  3. E. A. Rabiner
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  4. R. N. Gunn
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Corresponding author

Correspondence to D. R. Owen.

Ethics declarations

This review was not funded. This is a review paper, and as such no experiments were performed, and hence no animals or humans were involved and no approval was required.

Conflict of interest

D. R. Owen declares that he has no conflict of interest. Q. Guo declares that she has no conflict of interest. E. A. Rabiner declares that he has no conflict of interest. R. N. Gunn declares that he has no conflict of interest.

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Owen, D.R., Guo, Q., Rabiner, E.A. et al. The impact of the rs6971 polymorphism in TSPO for quantification and study design. Clin Transl Imaging 3, 417–422 (2015). https://doi.org/10.1007/s40336-015-0141-z

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  • DOI: https://doi.org/10.1007/s40336-015-0141-z

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