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Direct Monitoring of γ‐Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized 13 C‐Labeled Molecular Probe
Author(s) -
Nishihara Tatsuya,
Yoshihara Hikari A. I.,
aka Hiroshi,
Takakusagi Yoichi,
Hyodo Fuminori,
Ichikawa Kazuhiro,
Can Emine,
Bastiaansen Jessica A. M.,
Takado Yuhei,
Comment Arnaud,
Sando Shinsuke
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201603731
Subject(s) - in vivo , chemistry , enzyme , glutathione , biochemistry , biology , microbiology and biotechnology
The γ‐glutamyl transpeptidase (GGT) enzyme plays a central role in glutathione homeostasis. Direct detection of GGT activity could provide critical information for the diagnosis of several pathologies. We propose a new molecular probe, γ‐Glu‐[1‐ 13 C]Gly, for monitoring GGT activity in vivo by hyperpolarized (HP) 13 C magnetic resonance (MR). The properties of γ‐Glu‐[1‐ 13 C]Gly are suitable for in vivo HP 13 C metabolic analysis since the chemical shift between γ‐Glu‐[1‐ 13 C]Gly and its metabolic product, [1‐ 13 C]Gly, is large (4.3 ppm) and the T 1 of both compounds is relatively long (30 s and 45 s, respectively, in H 2 O at 9.4 T). We also demonstrate that γ‐Glu‐[1‐ 13 C]Gly is highly sensitive to in vivo modulation of GGT activity induced by the inhibitor acivicin.