NMR SPECTROSCOPY: TUMOR RADIATION RESPONSE PREDICTOR

本申请的主要目的是批判性地评估 体内31 P和1H NMR光谱法提供非侵入性， 肿瘤对放射治疗的反应的预测测定， 在治疗过程中。 由于NMR是非破坏性的， 在这些研究中开发和评价的方法学，使用小鼠肿瘤 系统，可应用于临床。 辐射的临床预测因子 应对措施应该：i）帮助选择临床试验组 针对放射抗性肿瘤的新治疗方案， 最大限度地提高识别有效治疗策略的概率; 和ii）允许个体患者的响应被用于 设计更有效的个性化治疗 一个特别强调的是放在审查之间的关系 放射生物学缺氧和NMR代谢特征。 体内 将通过NMR代谢的直接比较来检查关系 特征和放射生物学低氧分数测定在 相同的荷瘤小鼠。 捐款的存在和重要性 来自不具有放射生物学缺氧但具有 类似的NMR代谢特征，将通过以下方式进行评价：i）检查 核磁共振代谢特征与细胞代谢的关系 作为PO 2和所用时间长度的函数的放射敏感性 在允许NMR观察肿瘤的系统中的缺氧条件下， 在受控的、均匀的环境中的细胞（即，体外）;和ii） 检查坏死细胞的分数对关系的影响， NMR代谢特征与放射生物学缺氧之间的关系 在系统中的一个部分，它允许NMR观察肿瘤细胞在一个 模拟在肿瘤中发现的异质环境，但具有对照 在异质性程度上（即，在球状体中）。 低氧分数 从NMR和测量中获得的信息 放射性标记的米索硝唑结合将通过应用 同样的荷瘤小鼠。 核磁共振的预测能力 将通过比较个人的辐射反应进行评估 荷瘤小鼠的NMR代谢特征及其变化 在这些特征中，对治疗的反应，但在显著 肿瘤体积缩小。

The main objective of this application is to critically evaluate the potential for in vivo 31P and 1H NMR spectroscopy to provide a noninvasive, predictive assay of tumor response to radiation therapy before and/or during the course of treatment. Because NMR is nondestructive, the methodology developed and evaluated in these studies, using a murine tumor system, can be applied in the clinic. A clinical predictor of radiation response should: i) aid in the selection of groups for clinical trials of new treatment protocols targeted for radioresistant tumors thereby maximizing the probability of identifying effective treatment strategies; and ii) allow the response in individual patients to be utilized in designing more effective, individualized therapy. A special emphasis is placed on examining the relationship between radiobiological hypoxia and the NMR metabolic characteristics. The in vivo relationship will be examined by a direct comparison of the NMR metabolic characteristics and the radiobiological hypoxic fraction determined in the same tumor-bearing mice. The presence and importance of contributions to the NMR signal from cells which are not radiobiologically hypoxic, but have similar NMR metabolic characteristics, will be evaluated by: i) examining the relationship between the NMR metabolic characteristics and cellular radiosensitivity as a function of both PO2 and the length of time spent under hypoxic conditions in a system which allows NMR observation of tumor cells in a controlled, homogeneous environment (i.e., in vitro); and ii) examining the effects of the fraction of necrotic cells on the relationship between the NMR metabolic characteristics and the radiobiological hypoxic fraction in a system which allows NMR observation of tumor cells in a heterogeneous environment mimicing that found in tumors, but with control over the degre of heterogeneity (i.e., in spheroids). The hypoxic fraction information obtained from both NMR and measurement of radiolabeled-misonidazole binding will be compared by applying both techniques to the same tumor-bearing mice. The predictive ability of NMR will be evaluated by comparing the radiation response of individual tumor-bearing mice with their NMR metabolic characteristics and the changes in those characteristics in reponse to treatment, but before marked decreases in tumor size.