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Clinical Trial
. 2012 Jun;32(6):968-72.
doi: 10.1038/jcbfm.2012.46. Epub 2012 Apr 4.

Translocator protein (18 kDa) polymorphism (rs6971) explains in-vivo brain binding affinity of the PET radioligand [(18)F]-FEPPA

Romina Mizrahi  1 , Pablo M Rusjan, James Kennedy, Bruce Pollock, Benoit Mulsant, Ivonne Suridjan, Vincenzo De Luca, Alan A Wilson, Sylvain Houle
Affiliations
Clinical Trial

Translocator protein (18 kDa) polymorphism (rs6971) explains in-vivo brain binding affinity of the PET radioligand [(18)F]-FEPPA

Romina Mizrahi et al. J Cereb Blood Flow Metab. 2012 Jun.

Abstract

[(18)F]-FEPPA binds to the 18-kDa translocator protein (TSPO) and is used in positron emission tomography (PET) to detect microglial activation. However, quantitative interpretations of the PET signal with new generation TSPO PET radioligands are confounded by large interindividual variability in binding affinity. This presents as a trimodal distribution, reflecting high-affinity binders (HABs), low-affinity binder (LAB), and mixed-affinity binders (MABs). Here, we show that one polymorphism (rs6971) located in exon 4 of the TSPO gene, which results in a nonconservative amino-acid substitution from alanine to threonine (Ala147Thr) in the TSPO protein, predicts [(18)F]-FEPPA total distribution volume in human brains. In addition, [(18)F]-FEPPA exhibits clearly different features in the shape of the time activity curves between genetic groups. Testing for the rs6971 polymorphism may allow quantitative interpretation of TSPO PET studies with new generation of TSPO PET radioligands.

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Figures

Figure 1
Figure 1
Comparison of total distribution volume (VT) for high-affinity binders (HABs) and mixed-affinity binders (MABs) showing a significant difference between HABs and MABs (P<0.02) for all regions.
Figure 2
Figure 2
Comparison of averages time activity curves (TACs) in the prefrontal cortex for high-affinity binders (HABs) and mixed-affinity binders (MABs). The error bars represent the standard errors.
See this image and copyright information in PMC

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