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Title

Direct Monitoring of γ-Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized <sup>13</sup>C-Labeled Molecular Probe.

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

Abstract

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-[1-13C]Gly, for monitoring GGT activity in vivo by hyperpolarized (HP) 13C magnetic resonance (MR). The properties of γ-Glu-[1-13C]Gly are suitable for in vivo HP 13C metabolic analysis since the chemical shift between γ-Glu-[1-13C]Gly and its metabolic product, [1-13C]Gly, is large (4.3 ppm) and the T1 of both compounds is relatively long (30 s and 45 s, respectively, in H2O at 9.4 T). We also demonstrate that γ-Glu-[1-13C]Gly is highly sensitive to in vivo modulation of GGT activity induced by the inhibitor acivicin.

Subjects

GLUTATHIONE; HOMEOSTASIS; HYPERPOLARIZATION (Cytology); MEMBRANE potential; GLUTAMYL-tRNA synthetase

Publication

Angewandte Chemie International Edition, 2016, Vol 55, Issue 36, p10626

ISSN

1433-7851

Publication type

Academic Journal

DOI

10.1002/anie.201603731

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