MAGNETIC RESONANCE IMAGING OF GLUTATHIONE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们将测试谷胱甘肽对预测癌症治疗效果的有效性。谷胱甘肽存在于所有组织中，保护组织免受毒素的侵害。癌细胞利用谷胱甘肽的保护功能来保护细胞免受化疗的影响，因此耐药的癌症通常表现出高水平的谷胱甘肽。抗拒治疗是治疗未能治愈癌症的主要原因。因此，数十项临床研究表明，肿瘤组织活检标本中的谷胱甘肽可能是预测化疗反应的重要指标。以前，我们在4.7T使用质子去耦合的13C核磁共振来证明这种方法的可行性，这些数据被用来成功地获得R21拨款来支持这些研究。从那时起，我们一直在寻求提高SNR，并在11.1T上实施了类似的程序。线圈构造后遇到了相当大的问题，因为仪器没有针对13C进行适当的配置。此外，13C通道中存在明显的噪声，导致研究无效。这可以追溯到几个来源，最明显的是接收器一侧的过滤器。在布鲁克，马克·马丁利的帮助下，这个硬件已经修复或更换，我们的最新结果是令人满意的。在初步测试中，杜克大学准备的标记输液小鼠已经在体外进行了检查，并提供了令人鼓舞的结果，测量的信号具有足够的信噪比，可以进行基本的一维和二维光谱分析。我们现在正在为体内研究做准备

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