TY - JOUR
T1 - Direct Monitoring of γ-Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized13C-Labeled Molecular Probe
AU - Nishihara, Tatsuya
AU - Yoshihara, Hikari A.I.
AU - Nonaka, Hiroshi
AU - Takakusagi, Yoichi
AU - Hyodo, Fuminori
AU - Ichikawa, Kazuhiro
AU - Can, Emine
AU - Bastiaansen, Jessica A.M.
AU - Takado, Yuhei
AU - Comment, Arnaud
AU - Sando, Shinsuke
N1 - Funding Information:
This work was supported by CREST, the Japan Science and Technology Agency, the Centre d'Imagerie Biomédicale (CIBM) of the UNIL, UNIGE, HUG, CHUV, EPFL, and the Swiss National Science Foundation (grant PPOOP1_157547). The use of HyperSense was in part supported by the funding program “Creation of Innovation Centers for Advanced Interdisciplinary Research Areas” from JST. T.N. was funded by a fellowship from JSPS. We thank Prof. Masashi Tsuda and Mai Akakabe of Kochi University and Kaori Inoue of Kyushu University for their help in DNP-NMR measurements, and Dr. Carola Romero and Anne-Catherine Clerc for animal support in the in vivo experiments.
Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2016/8/26
Y1 - 2016/8/26
N2 - 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 HP13C 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 T1of 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.
AB - 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 HP13C 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 T1of 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.
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U2 - 10.1002/anie.201603731
DO - 10.1002/anie.201603731
M3 - Article
AN - SCOPUS:84983486477
SN - 1433-7851
VL - 55
SP - 10626
EP - 10629
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 36
ER -