ASSESSMENT OF HYPERTHERMIA BY IN VIVO NMR SPECTROSCOPY

热疗作为一种可行的肿瘤治疗方法的发展已经 由于缺乏足够的剂量测定而受阻。没有令人满意的身体状况 人们已经开发出表达“热剂量”的表达方式。此外，有了 目前的技术中，热分布往往是不均匀的，测温 不准确。这项申请旨在探索体内的有用性 表示热损伤的核磁共振(核磁共振)谱 生物学术语中的肿瘤。需要监测的核磁共振参数包括 从31P-核磁共振谱得出的ATP/PI比率和细胞内pH；以及 自旋-晶格弛豫时间(T1)，由1H-核磁共振波谱得出。这些 参数将在皮下注射RIF-1和 邓恩骨肉瘤。我们的假设是，这些物质中的通量 参数可以与各种重要的生物事件相关 肿瘤，并可用于监测热疗对代谢的影响 心理治疗。将进行的具体研究如下。 1.核磁共振参数变化与细胞杀伤的相关性。相关性 将寻求在ATP/PI或pH下降的程度与温度之间 克隆性细胞内容物(RIF-1，OS)或 循环肿瘤标志物(OS)。肿瘤的增加与肿瘤的关系 T1和热细胞杀灭也将被检测。 2.核磁共振参数变化与肿瘤血流量的相关性。这个 热致ATP、pH值下降与肿瘤丢失的关系 将检查血液流动情况。 3.核磁共振参数变化与细胞周期动力学的相关性 耐热性。亚致死后ATP、pH值逐渐恢复 体温过高将与热耐量的测量有关 (克隆形成试验)细胞周期动力学(DNA含量的FACS分析， 标签索引)。 4.根据前处理的核磁共振谱预测细胞杀伤率。的有用性 比较治疗前的pH、ATP/PI、肿瘤质量来预测细胞 用热气杀人。

The development of hyperthermia as a viable tumor treatment has been hindered by the lack of adequate dosimetry. No satisfactory physical expression has been developed to express "heat dose." Furthermore, with current techniques heat distribution is often inhomogenous and thermometry imprecise. This application seeks to explore the usefulness of in vivo nuclear magnetic resonance (NMR) spectroscopy to express thermal damage to tumors in biological terms. The NMR parameters to be monitored include the ratio ATP/Pi and intracellular pH, derived from 31P-NMR spectra; and the spin-lattice relaxation time (T1), derived from 1H-NMR spectroscopy. These parameters will be measured serially in mice with subcutaneous RIF-1 and Dunn osteosarcoma tumors. Our hypotheses are that the fluxes in these parameters can be related to a variety of important biologic events in the tumor, and can be used to monitor metabolic effects of hyperthermic therapy. Specific studies to be performed are as followed. 1. Correlation of change in NMR parameters with cell kill. Correlations will be sought between the degree of fall in ATP/Pi, or pH, with thermal cell kill as reflected in clonogenic cell content (RIF-1, OS) or circulating tumor marker (OS). The relationship between increase in tumor T1 and thermal cell kill will also be examined. 2. Correlation between change in NMR parameters and tumor blood flow. The relationship between thermally-induced fall in ATP, pH and loss of tumor blood flow will be examined. 3. Correlation between change in NMR parameters and cell cycle kinetics and thermal tolerance. The gradual recovery of ATP, pH seen after sublethal hyperthermia will be related to measurements of thermal tolerance (clonogenic assays) cell cycle kinetics (FACS analysis of DNA content, labelling index). 4. Prediction of cell kill from pretreatment NMR spectrum. Usefulness of pretreatment pH, ATP/Pi, tumor mass will be compared for prediction of cell kill with heat.