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

TY - JOUR

T1 - The impact of the rs6971 polymorphism in TSPO for quantification and study design

AU - Owen, D. R.

AU - Guo, Q.

AU - Rabiner, E. A.

AU - Gunn, R. N.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - PET imaging

KW - rs6971 polymorphism

KW - TSPO

UR - http://www.scopus.com/inward/record.url?scp=84952994214&partnerID=8YFLogxK

U2 - 10.1007/s40336-015-0141-z

DO - 10.1007/s40336-015-0141-z

M3 - Review article

AN - SCOPUS:84952994214

SN - 2281-5872

VL - 3

SP - 417

EP - 422

JO - Clinical and Translational Imaging

JF - Clinical and Translational Imaging

IS - 6

ER -