MAGNETIC RESONANCE IMAGING OF GLUTATHIONE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We will be testing the effectiveness of glutathione for predicting the effectiveness of cancer treatment. Glutathione is found in all tissue and protects the tissue from toxins. Cancer cells have used the glutathione protective function to shield cells from the effect of chemotherapy and thus cancers which are resistant to therapy often show high levels of glutathione. Resistance to therapy is the primary reason therapy fails to cure cancer. Therefore, dozens of clinical studies have shown that glutathione in tumor tissue biopsy samples may be an important predictor of response to chemotherapy. Previously we used proton decoupled 13C NMR at 4.7T to demonstrate the feasibility of this approach, and these data were used to successful obtain an R21 grant to support these studies. Since then we have been in search of improved SNR and have implemented similar procedures on the 11.1T. After coil construction considerable problems were encountered, since the instrument had not been appropriately configured for 13C. Additionally significant noise existed in the 13C channel making the studies ineffective. This has been traced to several sources, most notably the filters on the receiver side. With help from Bruker, Mark Mattingly specifically, this hardware has been fixed or replaced and our latest results are satisfactory. In a preliminary test, mice prepared at Duke with a label infusion have been examined ex vivo and provided encouraging results, with signals measured with enough SNR to allow rudimentary 1 and 2D spectroscopy. We are now preparing fro in vivo studies