MR Spectroscopy and Imaging of Sodium in Tumors

肿瘤中钠的磁共振波谱和成像

• 批准号: 6743790
• 负责人: NAVIN BANSAL
• 金额: $ 23.23万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6743790
• 关键词: MCF7 cell; atomic absorption spectrometry; bioenergetics; cell membrane; electrolyte balance; laboratory mouse; laboratory rat; magnetic resonance imaging; membrane transport proteins; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; neoplastic cell; neoplastic growth; nonhuman therapy evaluation; noninvasive diagnosis; nuclear magnetic resonance spectroscopy; sodium; technology /technique development

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.

描述（由申请人提供）：该项目的主要目的是 开发和评估使用多量子过滤（MQF）23NA磁性的使用 共振（MR）光谱（MRS）和成像（MRI）用于测量分隔 Na+在实验性肿瘤中，以最终可以应用该技术 临床。该项目的中心假设是MQF 23NA MR 技术可以提供完全无创的方法来监视和 肿瘤中跨膜钠梯度的成像异常。这 提案中概述的实验还将提供有关 跨膜钠梯度及其关系的生理作用 在未处理的生长过程中，透明的能量代谢和PHI，致敏 治疗和治疗的肿瘤。 提出了至少两种NMR方法来区分内部和 细胞外钠（NAI+和NAE+），使用顺磁性转移试剂 （SR）和MQF技术。我们介绍了产生的体内SR，TMDOTP5- 在肿瘤和其他组织中解析的NAI+和NAE+共振 对动物的毒性。但是，尚未安全使用的SR 可用的。我们的初步数据表明，尽管有些NAE+有助于 MQF 23NA信号在皮下植入的9L神经胶质瘤中，该信号为 缺血期间不会改变。如果在更一般的条件下这是真的，那么 MQF 23NA MR技术可以为 肿瘤中NAI+的监测和成像变化。 这项研究的第一个目标是确定是否可以使用MQF 23NA MRS 在更微妙的急性操纵过程中测量NAI+的变化。效果 操纵肿瘤能量代谢和离子交换机制的方法将是 研究。所选的操作用于使肿瘤敏化治疗。 我们的第二个目标是评估使用MQF 23NA MRS监测更改的使用 在慢性生理变化期间NAI+中。为此， 将研究未经治疗的肿瘤生长，放疗和化学疗法，并研究 MQF 23NA MRS/MRI的功效检测A的肿瘤反应 临床癌症化疗中使用的广泛的抗肿瘤剂 将在RIF-1和MCF-7肿瘤模型中进行研究。 拟议的23NA MR技术的开发将为 监视和成像NAI+可能在实验研究中有用 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 对于设计更有效的癌症治疗以及预测和 监测对治疗的反应。

项目成果

Predicting response to benzamide riboside chemotherapy in hepatocellular carcinoma using apparent diffusion coefficient of water.

• 发表时间: 2011-06
• 期刊: Anticancer research
• 影响因子: 2
• 作者: A. Babsky;S. Ju;B. George;S. Bennett;Mingsheng Huang;H. Jayaram;G. McLennan;N. Bansal