PERFLUOROCHEMICAL EMULSIONS AS ADJUNCTS TO RADIOTHERAPY

全氟化合物在1966年引起了广泛的关注，当时克拉克和 Gollan表明，当小鼠完全存活时，可以长时间存活 浸泡在液体中的全氟化学品，在大气中与O2平衡 压力。全氟化合物特殊的携氧能力具有 为全氟化合物生理乳剂的使用提供了依据 作为O2-转运液体在出血后或在手术期间血液 输血是不可能的，或者是被拒绝的。全氟化学治疗 乳剂(PFCE)和吸氧也可以减少心脏损伤 冠状动脉闭塞，预防急性局灶性脑缺血 结扎大脑动脉后，将脊髓损伤降至最低 脊髓受压，反映了氧气向缺血组织输送的改善。 实体瘤具有异常的、不足的血管，因此， 包含因一过性或慢性缺氧而出现的区域 血液流动不足。低氧细胞对 电离辐射的细胞毒性效应并限制其疗效 放射治疗在实现某些实体瘤局部控制方面的作用。我们发现 全氟化学乳剂和高氧的给药 大气增强BAlll2大鼠横纹肌肉瘤和EMT6的反应 对小鼠乳腺肿瘤进行放射治疗。据显示，这反映出 缺氧性肿瘤细胞的比例，而不是直接毒性或 PFCE的放射增敏作用。本项目将进一步研究 使用固体EMT6、KHJJ和BAlll2的这种效果的临床潜力 用来测试PFCE和氧气呼吸对肿瘤细胞的影响 生存曲线、肿瘤生长、肿瘤治愈和肿瘤氧合。这个 PFCE治疗对分次化疗疗效的影响 放射治疗和慢性低剂量率照射也将被检查。 高氟低氟交换输血的效果观察 血细胞，将会被检测。三氯甲烷的毒性和生理效应 PFCE/O2治疗及其对肿瘤生长的影响 还将检查转移情况。全氟辛烷烃类药物对环境的影响 几种正常组织(包括肺、皮肤、肝脏、 和造血系统)也将被研究。将使用这些数据 确定是否可以通过辅助性药物获得治疗收益 应用PFCE和氧气治疗，以进一步评估临床潜力 作为放射治疗的辅助手段的全氟化碳，并找出 在临床使用这些佐剂时可能会遇到。

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.