PERFLUOROCHEMICAL EMULSIONS AS ADJUNCTS TO RADIOTHERAPY

该项目长期目标是使用动物模型系统 评估全氟化学乳剂(PFC-E)作为 辅助放射治疗，并提供背景信息 需要设计和实施临床试验来测试这些试剂。这个 在这份五年续期申请中提出的研究将集中在 第二代PFC-E的研究，更具特点 比先导化合物更适合用作癌症治疗的辅助药物 (氟唑醇)用于我们最初的实验室研究和所有过去和 正在进行的临床试验。 对大鼠和小鼠移植肿瘤的研究将扩大到 评估更接近于这些患者的分步治疗方案 在临床放疗中的应用及最佳参数的确定 在这样的治疗方案中使用PFC-E。它的潜在价值 联合PFC-E和缺氧细胞增敏剂的多药方案或 对缺氧细胞有毒性的药物将进行检查，以评估是否使用 针对缺氧细胞的多种药物，这些药物可能以 不同的低氧细胞群，提供了更大的潜力 治疗效果。肿瘤观察变化的生物学基础 将检查响应，以评估除变化之外的其他因素 氧输送到肿瘤细胞对PFC-E的作用很重要。 第二代全氟化学乳剂对人体健康的影响 正常组织(骨髓、皮肤、肺和骨)的辐射响应 将进行检查，以便获得治疗收益的潜力 可以用这些药剂进行评估。这些PFC-E对肿瘤的影响 还将检查成长和进步，以确保这些 药物对恶性肿瘤没有意想不到的影响。来自这些网站的数据 研究将被用来帮助设计第二次临床试验 新一代PFC-E作为放射治疗的辅助手段。

The long rang goal of this project is to use animal model systems to evaluate the potential value of perfluorochemical emulsions (PFC-E) as adjuncts to radiotherapy and to provide the background information needed to design and implement clinical rials testing these agents. The studies proposed in this five year renewal application will focus on studies of second generation PFC-E, having characteristics more appropriate for use as adjuncts to cancer therapy than the lead compound (Fluosol) used in our initial laboratory studies and in all past and ongoing clinical trials. Studies with transplanted tumors in rats and mice will be extended to assess fractionated treatment regimens which more closely model those used in clinical radiotherapy and to determine the optimal parameters for administering PFC-E during such regimens. The potential value of multi-agent regimens combining PFC-E with hypoxic cell sensitizers or drugs toxic to hypoxic cells will be examined, to assess whether the use of multiple agents directed against hypoxic cells, which may target different hypoxic cell populations, offer the potential for greater therapeutic benefit. The biological bases of observed changes in tumor response will be examined, to assess whether factors other than changes O2 delivery to tumor cells are important to the effects of the PFC-E. Effects of second generation perfluorochemical emulsions on the radiation responses of normal tissues (bone marrow, skin, lung and bone) will be examined so that the potential for obtaining therapeutic gain with these agents can be assessed. The effects of these PFC-E on tumor growth and progression will also be examined, to ensure that these agents have no unexpected effects on the malignancies. Data from these studies will be used to help design clinical trials testing second generation PFC-E as adjuncts to radiotherapy.