Conference Paper Application of a novel 13C hyperpolarized metabolic tracer for gamma-Glutamyl transferase activity in vivo tumor xenograft

Seki, Tomohiro  ,  Itoda, Marino  ,  Kishimoto, Shun  ,  Yamamoto, Kazu  ,  Takakusagi, Yoichi  ,  Brender, Jeffery  ,  M. Malinowski, Ronja  ,  Nishihara, Tatsuya  ,  A.I. Yoshihara, Hikari  ,  Nonaka, Hiroshi  ,  Saito, Keita  ,  Oshima, Nobu  ,  Jan, H. Ardenkjaer-Larsen  ,  B. Mitchell, James  ,  C. Krishna, Murali  ,  Sando, Shinsuke

γ-Glutamyl transferase (GGT) is membrane-bound enzyme that catalyzes the cleavage of γ-glutamyl moiety of extracellular glutathione to supply cysteine for intracellular synthesis of glutathione as anti-oxidant. Elevated GGT activity has been found in wide range of cancers, where GGT promotes tumor cell survival, tumor progression, and resistance to radiotherapy and chemotherapies. Based on biological and clinical studies, we hypothesize that non-invasive methods for real-time monitoring of GGT activity will provide the information of cancer characterization, prognosis, and development of therapeutic strategy.Hyperpolarized (HP) 13C Magnetic Resonance spectroscopy (MRS) and imaging which have been newly developed modality enable non-invasive molecular imaging of real-time metabolism in tumor. Despite of the advantageous feature, only a limited number of 13C-labeled probes have been utilized for in vivo applications because of their physicochemical property. Dr. Nishihara et al., however, have successfully designed and prepared a novel HP molecular probe for GGT activity, γ-Glu-[1-13C]Gly. γ-Glu-[1-13C]Gly was designed to produce a distinct 13C signal in chemical shift range by the enzymatic cleavage, due to the positively charged amino group of released [1-13C]Gly in physiological pH. It was demonstrated that this probe can monitor real-time GGT activity in vivo rat kidney as well as in vitro homogenate samples.Herein, we investigated to apply this novel probe with HP-MRS technology to in vivo tumor xenograft.

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