The impact of the rs6971 polymorphism in TSPO for quantification and study design
File(s)
Accepted version
Author(s)
Owen, DR
Guo, Q
Rabiner, EA
Gunn, RN
Type
Journal Article
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.
Date Issued
2015-10-15
Date Acceptance
2015-08-28
Citation
Clinical and Translational Imaging, 2015, 3 (6), pp.417-422
ISSN
2281-5872
Publisher
Springer
Start Page
417
End Page
422
Journal / Book Title
Clinical and Translational Imaging
Volume
3
Issue
6
Copyright Statement
The final publication is available at Springer via https://dx.doi.org/10.1007/s40336-015-0141-z
Sponsor
The Academy of Medical Sciences
Grant Number
n/a
Publication Status
Published