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被证明是可行的。 由于缺乏足够的剂量测定而受阻。 没有令人满意的体格检查 已经发展了表达式来表示“热剂量”。“此外，随着 目前的技术热分布通常是不均匀的， 不精确。 本申请旨在探索体内 核磁共振（NMR）光谱来表达热损伤， 肿瘤在生物学上 待监测的NMR参数包括 ATP/Pi比率和细胞内pH，源自31 P-NMR光谱;以及 自旋-晶格弛豫时间（T1），来源于1H-NMR光谱。 这些 将在皮下注射RIF-1的小鼠中连续测量参数， Dunn骨肉瘤 我们的假设是， 参数可以与各种重要的生物事件， 肿瘤，并可用于监测代谢的影响， 疗法 待进行的具体研究如下。 1. NMR参数变化与细胞杀伤的相关性。 相关性 将在ATP/Pi或pH的下降程度与热之间寻找 克隆形成细胞含量（RIF-1，OS）反映的细胞杀伤，或 循环肿瘤标志物（OS）。 肿瘤的增加与 还将检查T1和热细胞杀灭。 2.核磁共振参数变化与肿瘤血流量的相关性。 的 热诱导ATP、pH下降与肿瘤消失的关系 将检查血流。 3. NMR参数变化与细胞周期动力学之间的相关性， 耐热性 亚致死后ATP、pH逐渐恢复 体温过高将与热耐受性的测量有关 （克隆形成测定）细胞周期动力学（DNA含量的FACS分析， 标签索引）。 4.根据预处理NMR光谱预测细胞杀伤。 有用 将比较治疗前pH、ATP/Pi、肿瘤质量，以预测细胞凋亡。 用热杀死。

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.