Noninvasive In vivo Detection of Glutathione Metabolism in Tumors (2005)

Author(s): Thelwall PE, Yemin AY, Gillian TL, Simpson NE, Kasibhatla MS, Rabbani ZN, MacDonald JM, Blackband SJ, Gamcsik MP

    Abstract: Magnetic resonance spectroscopic imaging has been used to follow glutathione metabolism and evaluate glutathione heterogeneity in intact tumor tissue. Stable isotope-labeled glutathione was detected in s.c. implanted fibrosarcoma tumors in anesthetized rats following infusion of [2-13C]glycine. Using 1H-decoupled 13C magnetic resonance spectroscopy, the appearance of [2-13C]glycine at 42.4 ppm and the subsequent incorporation of this isotope label into the glycyl residue of glutathione at 44.2 ppm can be detected. The identity and relative concentrations of labeled metabolites observed in the in vivo spectrum were confirmed in studies of tissue extracts. The high level of isotopic enrichment and the concentration of glutathione in tumor tissue allow for collection of spatially localized spectra using 13C chemical shift imaging methods. These data provide the first direct images of glutathione in intact tumor tissue and show metabolic heterogeneity. This method may lead to the ability to monitor changes in tumor tissue redox state that may ultimately affect diagnosis, monitoring, and treatment.

      • Date: 15-11-2005
      • Journal: Cancer Research
      • Volume: 65
      • Issue: 22
      • Pages: 10149-10153
      • Publisher: American Association for Cancer Research
      • Publication type: Article
      • Bibliographic status: Published

      Keywords: Animals Carbon Radioisotopes/diagnostic use Female Fibrosarcoma/*metabolism Glutathione/biosynthesis/*metabolism Glycine/metabolism Nuclear Magnetic Resonance, Biomolecular/*methods Protons Rats Rats, Inbred F344 Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.


      Dr Peter Thelwall
      William Leech Reader in Magnetic Resonance Physics