Direct Monitoring of γ-Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized (13) C-Labeled Molecular Probe

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 hype...

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Published in:Angewandte Chemie International Edition 2016-08, Vol.55 (36), p.10626-10629
Main Authors: Nishihara, Tatsuya, Yoshihara, Hikari A I, Nonaka, Hiroshi, Takakusagi, Yoichi, Hyodo, Fuminori, Ichikawa, Kazuhiro, Can, Emine, Bastiaansen, Jessica A M, Takado, Yuhei, Comment, Arnaud, Sando, Shinsuke
Format: Article
Language:English
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Summary: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 T1 of both compounds is relatively long (30 s and 45 s, respectively, in H2 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.
ISSN:1521-3773
DOI:10.1002/anie.201603731