title: Direct Monitoring of γ-Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized (13) C-Labeled Molecular Probe.
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-(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.
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nishihara
authors.affiliation: Institute of Physics of Biological Systems, École Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland.
authors.forename: Hikari A I
authors.initials: HA
authors.lastname: Yoshihara
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonaka
authors.affiliation: Incubation Center for Advanced Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takakusagi
authors.affiliation: Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Hyodo
authors.affiliation: Incubation Center for Advanced Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.|Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ichikawa
authors.affiliation: Institute of Physics of Biological Systems, École Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland.
authors.forename: Emine
authors.initials: E
authors.lastname: Can
authors.affiliation: Institute of Physics of Biological Systems, École Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland.
authors.forename: Jessica A M
authors.initials: JA
authors.lastname: Bastiaansen
authors.affiliation: Institute of Physics of Biological Systems, École Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland.|Department of Functional Brain Imaging Research, Brain and Mind Research Team, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Chiba, 263-8555, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Takado
authors.affiliation: Institute of Physics of Biological Systems, École Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland. arnaud.comment@epfl.ch.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Comment
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan. ssando@chembio.t.u-tokyo.ac.jp.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Sando
mesh_terms: D000818:Animals; D057075:Enzyme Assays / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D015335:Molecular Probes / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D007555:Isoxazoles; D015335:Molecular Probes; D005723:gamma-Glutamyltransferase; D005978:Glutathione; C006303:acivicin
keywords: NMR spectroscopy; biosensors; dynamic nuclear polarization; hyperpolarization; γ-glutamyl transpeptidase