PERFLUOROCHEMICAL EMULSIONS AS ADJUNCTS TO RADIOTHERAPY

全氟化学乳剂作为放射治疗的辅助剂

• 批准号: 3172835
• 负责人: SARA ROCKWELL
• 金额: $ 23.79万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-05-01 至 1987-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3172835
• 关键词: fluorescent dye /probe; neoplasm /cancer radiation therapy; perfusion; radiation dosage; radiation sensitivity; radiation therapy dosage; respiratory oxygenation

Perfluorochemicals attracted widespread attention in 1966, when Clark and Gollan showed that mice could survive for prolonged periods when completely immersed in liquid perfluorochemicals equilibriated with 02 at atmospheric pressure. The exceptional 02-carrying capacity of perfluorochemicals has provided the basis for testing these compounds for the perfusion of organs to be transplanted and as 02-transport fluids for use after hemorrhage or during surgery when blood transfusions are impossible or refused. Recent studies have shown that treatment with perfluorochemical emulsions and 02 can reduce ischemic myocardial damage after coronary artery occlusion, can protect against acute focal cerebral ischemia after ligation of the crebral artery, and can minimize injury after spinal cord compression. This is thought to reflect improved 02 delivery into the ischemic tissues, resulting from the unusual 02-transport capacity of the perfluorocarbons, perfluorochemical-induced changes in blood viscosity, and the small size of the micelles, which can enter-regions inaccessible to red blood cells. Solid tumors possess abnormal and insufficient vasculatures and, as a result, contain areas which are hypoxic because of transient or chronic deficiencies in blood flow. Hypoxic cells are very resistant to the cytotoxic effects of ionizing radiation and may limit the efficacy of radiotherapy in curing tumors. If administration of perfluorochemical emulsions and 02 can improve oxygenation in the hypoxic areas of tumors, in a manner analogous to that observed in other ischemic tissues, these agents may increase the radiosensitivity of some hypoxic tumor cells and improve the results of radiotherapy. This project will examine this hypothesis. EMT6 and KHJJ mouse mammary tumors and BA1112 rat rhabdomyosarcomas will be used to test the effects of perfluorochemical emulsions and 02-breathing on tumor cell survival curves, hypoxic fractions, and tumor cure. The effect of treatment with perfluorochemical emulsions on the efficacy of fractionated radiotherapy and chronic low dose rate irradiation will also be examined. The effect of the agents on the radiation response of 3 normal tissues (skin, gut, and bone marrow) will also be studied. These data will be used to calculate therapeutic ratios and assess the clinical potential of perfluorochemical emulsions as adjuncts to radiotherapy.

1966年，全氟化学品引起了广泛关注，当时克拉克和 Gollan表明，当小鼠完全存活时， 浸没在与O2在大气压下平衡的液体全氟化合物中 压力 全氟化学品特殊的氧气携带能力， 为测试这些化合物的器官灌注提供了基础 移植和作为O2-运输流体用于出血后使用，或 在手术期间，输血是不可能的或被拒绝。 最近 研究表明，用全氟化学品乳液和O2 可减轻冠状动脉闭塞后缺血性心肌损伤， 结扎大鼠大脑中动脉对急性局灶性脑缺血的保护 动脉，并可以减少脊髓压迫后的损伤。 这是 被认为反映了改善的O2输送到缺血组织中， 这是由于全氟化碳的不寻常的O2传输能力， 全氟化学品引起的血液粘度变化，以及 胶束，它可以进入红细胞无法到达的区域。 实体瘤具有异常和不足的血管， 结果，包含由于短暂或慢性缺氧的区域 血液流动不足。 低分化细胞对 电离辐射的细胞毒性效应，并可能限制 放射疗法治疗肿瘤。 如果施用全氟化学品， 乳剂和O2可以改善肿瘤缺氧区域的氧合， 类似于在其他缺血组织中观察到的方式，这些药剂 可能会增加某些缺氧肿瘤细胞的放射敏感性， 放疗的结果。 本项目将检验这一假设。 EMT6和KHJJ小鼠乳腺肿瘤和BA1112大鼠横纹肌肉瘤将在 用于测试全氟化学品乳剂和氧气呼吸对 肿瘤细胞存活曲线、缺氧分数和肿瘤治愈。 效果 全氟化学乳剂治疗的疗效 分次放疗和慢性低剂量率照射也将 接受检查。 本文研究了三种药物对小鼠辐射反应的影响。 还将研究正常组织（皮肤、肠和骨髓）。 这些 数据将用于计算治疗比率并评估临床 全氟化学乳剂作为放射治疗药物的潜力。