MR Spectroscopy and Imaging of Sodium in Tumors

描述（由申请人提供）：本项目的主要目标是 开发和评估使用多量子滤波（MQF）23 Na磁性 共振（MR）波谱（MRS）和成像（MRI），用于测量房室 Na+的实验肿瘤，使技术可能最终应用于 临床上本项目的中心假设是MQF 23 Na MR 技术可以提供完全非侵入性的监测方法， 肿瘤中跨膜钠梯度的成像异常。的 提案中概述的实验还将提供有关 跨膜钠梯度的生理作用及其相互关系 在未经处理的生长期间，细胞能量代谢和pHi，致敏 治疗和治疗。 已经提出了至少两种NMR方法来区分内部和内部之间的差异。 细胞外钠（Nai+和Nae+），使用顺磁位移试剂 (SR)MQF技术。我们引入了体内SR，TmDOTP 5-，其产生 在肿瘤和其他组织中消除Nai+和Nae+共振， 对动物的毒性。然而，对人类安全使用的SR还没有 available.我们的初步数据显示，虽然，一些Nae+有助于 皮下植入的9 L胶质瘤中的MQF 23 Na信号，该信号不 在缺血期间不改变。如果在更一般的条件下这是真的，那么 MQF 23 Na MR技术可以提供完全无创的方法， 监测和成像肿瘤中Nai+的变化。 本研究的第一个目标是确定是否可以使用MQF 23 Na MRS 以测量Nai+在更微妙的急性操作期间的变化。的影响 操纵肿瘤的能量代谢和离子交换机制， 研究了所选择的操作用于使肿瘤对治疗敏感。 我们的第二个目标是评估MQF 23 Na MRS用于监测变化的使用 在慢性生理变化期间的Nai+。为此， 未经治疗的肿瘤生长，放疗和化疗将进行研究， MQF 23 Na MRS/MRI检测肿瘤化疗反应的有效性 用于临床癌症化疗的广泛的抗肿瘤剂 将在RIF-1和MCF-7肿瘤模型中进行研究。 所提出的23 Na MR技术的发展将提供以下方法： 监测和成像Nai+，可能证明在实验研究中有用， 肿瘤和癌症的临床管理。此外，拟议的研究 将增强对肿瘤中钠生理学的理解，这可能证明 可用于设计更有效的癌症治疗，并用于预测和 监测对治疗的反应。

DESCRIPTION (provided by applicant): The main objective of this project is to develop and evaluate the use of multiple-quantum-filtered (MQF) 23Na magnetic resonance (MR) spectroscopy (MRS) and imaging (MRI) for measuring compartmental Na+ in experimental tumors so that the techniques may eventually be applied clinically. The central hypothesis in this project is that MQF 23Na MR techniques can provide completely noninvasive methods for monitoring and imaging abnormalities in transmembrane sodium gradients in tumors. The experiments outlined in the proposal will also provide information about the physiological role of the transmembrane sodium gradient and its relationship with cellular energy metabolism and pHi during untreated growth, sensitization of tumors to therapy and therapy. At least two NMR methods have been proposed to distinguish between intra- and extracellular sodium (Nai+ and Nae+), the use of paramagnetic shift reagents (SR) and MQF techniques. We introduced the in vivo SR, TmDOTP5-, which produces resolved Nai+ and Nae+ resonance in tumors and other tissues with minimal toxicity to the animal. However, an SR safe for use in humans is not yet available. Our preliminary data shows that although, some Nae+ contributes to the MQF 23Na signal in the subcutaneously implanted 9L glioma, this signal does not change during ischemia. If this is true under more general conditions, then MQF 23Na MR techniques can provide completely noninvasive methods for monitoring and imaging changes in Nai+ in tumors. The first goal of this study is to determine whether MQF 23Na MRS can be used to measure changes in Nai+ during more subtle acute manipulations. The effects of manipulating the tumor energy metabolism and ion exchange mechanisms will be studied. The chosen manipulations are used for sensitizing tumor to therapy. Our second goal is to evaluate the use of MQF 23Na MRS for monitoring changes in Nai+ during chronic physiological changes. For this purpose, effects of untreated tumor growth, radiotherapy and chemotherapy will be studied and the efficacy of MQF 23Na MRS/MRI for detecting tumor response to chemotherapy by a broad range of antineoplastic agents employed in clinical cancer chemotherapy will be investigated in RIF-1 and MCF-7 tumor models. The development of proposed 23Na MR techniques will provide methods for monitoring and imaging Nai+ that may prove useful in experimental studies of tumors and clinical management of cancer. In addition, the proposed research will enhance the understanding of sodium physiology in tumors, which may prove useful for designing more effective cancer treatment, and for predicting and monitoring response to therapy.