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: 3172838
• 负责人: SARA ROCKWELL
• 金额: $ 24.24万
• 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 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3172838
• 关键词: breast neoplasms; fluorescent dye /probe; hypoxia; ionizing radiation; laboratory mouse; laboratory rat; neoplasm /cancer radiation therapy; oxygen transport; perfusion; radiation sensitivity; respiratory oxygenation; rhabdomyosarcoma

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 O2 at atmospheric pressure. The exceptional O2-carrying capacity of perfluorochemicals has provided the basis for using physiolologic emulsions of perfluorochemicals as O2-transport fluids after hemorrhage or during surgery when blood transfusions are impossible or refused. Treatment with perfluorochemical emulsions (PFCE's) and O2-breathing also reduces myocardial damage after coronary artery occlusion, protects against acute focal cerebral ischemia after ligation of the cerebral artery, and minimizes injury after spinal cord compression, reflecting improving O2 delivery into ischemic tissues. Solid tumors have abnormal, 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 limit the efficacy of radiotherapy in achieving local control of some solid tumors. We found that administration of a perfluorochemical emulsion and a high-oxygen atmosphere increases the response of BAlll2 rat rhabdomyosarcomas and EMT6 mouse mammary tumors to radiation. This was shown to reflect a decrease in the proportion of hypoxic tumor cells, rather than a direct toxic or radiosensitizing effect of the PFCE. This project will examine further the clinical potential of this effect, using solid EMT6, KHJJ, and BAlll2 tumors to test the effects of PFCE's and O2-breathing on tumor cell survival curves, tumor growth, tumor cure, and tumor oxygenation. The effect of treatment with PFCE's on the efficacy of fractionated radiotherapy and chronic low dose rate irradiation will also be examined. The effects of exchange transfusions, producing high flurocrits and low hematocrits, will be tested. The toxicities and physiological effects of the PFCE/O2 treatments and the effects of the treatments on tumor growth and metastasis will also be examined. The effects of PFCE's on the radiation responses of several normal tissues (including lung, skin, liver, and the hematopoetic system) will also be studied. These data will be used to determine whether therapeutic gain can be obtained by adjunctive treatment with PFCE's and oxygen, to assess further the clinical potential of PFCE's as adjuncts to radiotherapy, and to identify any problems which may be encountered in the clinical use of these adjuvants.

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， 浸泡在与氧气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， 为使用全氟化合物的生理乳液提供了基础 作为出血后或手术过程中的氧气运输液体， 输血是不可能的或被拒绝的。 用全氟化合物处理 乳剂（PFCE）和O2呼吸也可以减少心肌损伤后， 冠状动脉闭塞，防止急性局灶性脑缺血 结扎脑动脉后，并尽量减少脊髓损伤后， 脊髓压迫，反映改善了向缺血组织的O2输送。 实体瘤具有异常的、不足的血管，因此， 包含因短暂或慢性缺氧而缺氧的区域 血液流动不足。 低分化细胞对 电离辐射的细胞毒性效应，并限制 放疗在某些实体瘤的局部控制中的应用。 我们发现 使用全氟化学乳剂和高氧 大气增加BA 1112大鼠横纹肌肉瘤和EMT 6的反应 小鼠乳腺肿瘤放射治疗。 这表明， 低氧肿瘤细胞的比例，而不是直接毒性或 PFCE的放射增敏作用。 本项目将进一步审查 使用固体EMT 6、KHJJ和BA 1112， 肿瘤，以测试PFCE和O2呼吸对肿瘤细胞的影响 存活曲线、肿瘤生长、肿瘤治愈和肿瘤氧合。 的 PFCE治疗对分次给药疗效的影响 放射治疗和慢性低剂量率照射也将进行检查。 交换输血的影响，产生高氟氯特和低氟氯特， 血细胞比容，将被测试。 的毒性和生理效应 PFCE/O2治疗以及治疗对肿瘤生长的影响 还将检查转移。 PFCE的影响， 几种正常组织（包括肺，皮肤，肝， 和造血系统）也将被研究。 这些数据将用于 为了确定是否可以通过抑制性治疗获得治疗增益， 用PFCE和氧气治疗，以进一步评估临床潜力 的PFCE的作为替代放疗，并确定任何问题， 在这些佐剂的临床应用中可能会遇到。