NMR SPECTROSCOPY: TUMOR RADIATION RESPONSE PREDICTOR

此应用程序的主要目标是批判性地评估 体内31P和1H核磁共振波谱有可能提供一种无创、 肿瘤放射治疗前和/或治疗反应的预测分析 在治疗过程中。因为核磁共振是非破坏性的，所以 在这些研究中开发和评估的方法，使用了一种小鼠肿瘤 系统，可应用于临床。辐射的临床预测指标 应对措施应：i)协助选择用于临床试验的小组 因此，针对放射抵抗肿瘤的新治疗方案 最大限度地提高确定有效治疗策略的可能性； 以及二)允许个别患者的反应用于 设计更有效的个性化治疗。 特别强调的是考察两者之间的关系。 放射性生物缺氧与核磁共振代谢特征。活体内 关系将通过核磁共振代谢的直接比较来检验 放射性生物低氧组分的特征和测定 同样的荷瘤小鼠。贡献的存在和重要性 来自细胞的核磁共振信号不是放射性生物缺氧的，但有 类似的核磁共振代谢特征将通过以下方式进行评估：i)检查 核磁共振代谢特性与细胞的关系 放射敏感性与氧分压和停留时间长短的关系 在允许核磁共振观察肿瘤的系统中的低氧条件下 细胞在受控、均匀的环境中(即，在体外)；以及ii) 检测坏死细胞的比例对这种关系的影响 核磁共振代谢特征与放射性生物缺氧的关系 一种允许核磁共振观察肿瘤细胞的系统中的组份 在肿瘤中发现的异质环境，但有对照 超过了异质性的程度(即，在椭球体中)。低氧部位 从核磁共振和测量中获得的信息 放射性标记-咪唑结合将通过应用两种方法进行比较 技术应用于相同的荷瘤小鼠。核磁共振的预测能力 将通过比较个人的辐射反应来进行评估 荷瘤小鼠核磁共振代谢特征及其变化 在那些治疗反应的特征上，但在标记之前 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.