OXYGEN LEVELS AND RADIOSENSITIVITY IN TUMORS

肿瘤中的氧水平和放射敏感性

• 批准号: 6137602
• 负责人: DAVID F WILSON
• 金额: $ 22.21万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-16 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6137602
• 关键词: blood /plasma substitute; disease /disorder model; infrared spectrometry; intravenous administration; laboratory rat; misonidazole; neoplasm /cancer blood supply; neoplasm /cancer radiation therapy; neoplastic growth; nonhuman therapy evaluation; oxygen tension; phosphorescence; polyethylene glycols; porphyrins; radiation sensitivity

DESCRIPTION: Quantitative, real time measurements of the oxygen pressure in tumors in vivo and in vitro will be used to determine the degree of hypoxia and its relationship to radiation sensitivity. The measurements will compare three independent methods for measuring oxygen in tissue, focusing on a new optical technique, oxygen dependent quenching of phosphorescence. O2 levels and treatment induced alterations in these levels, oxygen pressure distributions (histograms) in the tissue, and two and three dimensional maps of these oxygen distributions in the tissue will all be measured. Three important hypotheses will be tested. 1.Phosphorescence measurements permit detection of small tumors by the abnormal distributions of blood and oxygen pressures which are present within the tumors. 2. Phosphorescence measurements make it possible to quantitate the oxygen distribution in tumors and to evaluate, in real time, the efficacy of interventions designed to alter these oxygen levels. 3. The oxygen pressure in the tissue is critically important to radiation therapy and increased oxygen pressure in the tumor increases the fraction of cells killed by a dose of radiation. Our research program will: A. Quantitate the oxygen pressure in the blood within tumors and the surrounding tissue during the growth and development of the tumors. B. Quantitate the oxygen dependence of tumor response to radiation therapy and its response to interventions designed to alter tumor metabolism and physiology. C. Extend the phosphorescence quenching measurements to three dimensions by optically sectioning using different wavelengths of excitation light, thereby improving resolution of the distribution of oxygen and blood in the vasculature. D. Evaluate new phosphors for oxygen measurement in biological materials, with emphasis on those which absorb and phosphoresce in the near infra red region of the spectrum. The Pd-tetrabenzoporphyrin structure is being chemically modified to provide phosphors which are water soluble and with calibrations insensitive to alterations in their environment (pH, ionic strength, albumin concentration). Phosphors will be selected which can be injected intravenously and then, after the oxygen measurements, are excreted by the kidney.

描述：氧气压力的定量、真实的时间测量， 体内和体外的肿瘤将被用来确定缺氧的程度 以及它与辐射敏感性的关系。 测量结果将 比较三种测量组织中氧气的独立方法，聚焦 一种新的光学技术，氧依赖的磷光猝灭。 O2水平和处理诱导的这些水平、氧分压 组织中的分布（直方图）以及二维和三维图 这些组织中的氧分布都将被测量。 三 重要的假设将得到检验。 1.磷光测量允许 通过血液和氧气的异常分布检测小肿瘤 肿瘤内存在的压力。 2. 磷光 测量使得有可能定量氧气分布， 并在真实的时间内评估设计的干预措施的有效性 来改变氧气含量 3. 组织中的氧分压 对放射治疗至关重要， 肿瘤增加了被辐射剂量杀死的细胞的分数。 我们的研究计划将：A.定量血液中的氧分压 在生长和发育过程中， 的肿瘤。 B。定量肿瘤对氧的依赖性 放射治疗及其对旨在改变肿瘤的干预措施的反应 新陈代谢和生理学。 C.延长磷光猝灭 通过使用不同的光学切片进行三维测量 波长的激发光，从而提高了分辨率 氧气和血液在脉管系统中的分布。 D.评估新 生物材料中氧测量用荧光粉，重点是 那些吸收和磷光在近红外区的 江西篇章 Pd-四苯并卟啉结构被化学修饰以提供 水溶性磷光体，其校准对 环境的改变（pH、离子强度、白蛋白 浓度）。 将选择可注入的磷光体 静脉注射，然后，在氧测量后，由 肾