Translocator Protein (18 kDa) Polymorphism (rs6971) Explains in-vivo Brain Binding Affinity of the PET Radioligand [18F]-FEPPA | Zendy

Romina Mizrahi | Zendy; Pablo Rusjan | Zendy; James L. Kennedy | Zendy; Bruce G. Pollock | Zendy; Benoit H. Mulsant | Zendy; Ivonne Suridjan | Zendy; Vincenzo De Luca | Zendy; Alan A. Wilson | Zendy; Sylvain Houle | Zendy

Open Access

Translocator Protein (18 kDa) Polymorphism (rs6971) Explains in-vivo Brain Binding Affinity of the PET Radioligand [¹⁸F]-FEPPA

Author(s) -

Romina Mizrahi,

Pablo Rusjan,

James L. Kennedy,

Bruce G. Pollock,

Benoit H. Mulsant,

Ivonne Suridjan,

Vincenzo De Luca,

Alan A. Wilson,

Sylvain Houle

Publication year - 2012

Publication title -

journal of cerebral blood flow and metabolism

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.167

H-Index - 193

eISSN - 1559-7016

pISSN - 0271-678X

DOI - 10.1038/jcbfm.2012.46

Subject(s) - translocator protein , radioligand , positron emission tomography , in vivo , chemistry , positron , microbiology and biotechnology , receptor , biology , biochemistry , neuroscience , genetics , physics , immunology , microglia , quantum mechanics , electron , inflammation

[(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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