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Development of Novel Sensitizer to Improve Response of Hypoxic Tumors to Radiatio

开发新型敏化剂以改善缺氧肿瘤对放射的反应

基本信息

批准号：
7808142
负责人：
Evan charles Unger
金额：
$ 20.44万
依托单位：
NUVOX PHARMA, LLC
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-24 至 2010-11-23
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Tissue probe measurements and imaging show that tumor hypoxia is common in many cancers including head and neck cancer, cervical cancer, prostate cancer and many other solid tumors. Tumors with low oxygen concentrations are resistant to radiation treatment. New imaging techniques can be used to diagnose tumor hypoxia. A number of methods have been tested to increase tumor oxygenation, but in general without great success. There is as yet no clinically available method of increasing tumor oxygenation to improve response to radiation treatment. The purpose of this Phase I SBIR grant application is to develop a new oxygen carrier based upon dodecaperfluoropentane emulsion (DDFPe) that is active at less than 1/00th the dose of previously described carriers and that will clear from the body shortly after radiation treatment. The Specific Aims are: 1. Develop an optimized DDFPe radiation sensitizer formulation; 2. Characterize the formulation in vitro; 3. Study toxicity/biocompatibility in cell culture; 4. Conduct toxicity studies in mice; 5. Perform radiation sensitization studies in cell culture. DDFPe was previously studied in man for another application, but the surfactant used to stabilize the emulsion was not pure. We have synthesized pure surfactants for stabilizing DDFPe that should be pharmaceutically acceptable. The experiments are designed to test and compare these new surfactants for stabilizing DDFPe. From these preliminary studies we will define prototype DDFPe radiation sensitization product for formal preclinical development. In Phase II we shall conduct animal studies in which we will use imaging to show amelioration in tumor hypoxia pre and post treatment and improvement in tumor response with radiation therapy for hypoxic tumors. PUBLIC HEALTH RELEVANCE: Tumor hypoxia is common in many cancers including head and neck cancer, cervical cancer, prostate cancer and many other solid tumors. Tumors with low oxygen concentrations are resistant to radiation treatment. This NIH Phase I grant application is directed to development of a new sensitizer that may be much more effective than prior compounds in improving oxygenation of hypoxic cancer cells and improving response of cancer to treatment.

描述(申请人提供)：组织探针测量和成像显示，肿瘤缺氧在许多癌症中都很常见，包括头颈癌、宫颈癌、前列腺癌和许多其他实体肿瘤。氧浓度低的肿瘤对放射治疗有抵抗力。新的成像技术可以用来诊断肿瘤缺氧。已经测试了许多方法来增加肿瘤的氧合，但总的来说都不是很成功。到目前为止，还没有临床上可用的方法来增加肿瘤的氧合来改善对放射治疗的反应。这项第一阶段SBIR资助申请的目的是开发一种基于十二氟戊烷乳剂(DDFPe)的新氧载体，其活性低于前面描述的载体剂量的1/00，并将在放射治疗后不久从体内清除。具体目标是：1.开发优化的DDFPe辐射增敏剂配方；2.体外表征该配方；3.在细胞培养中研究毒性/生物相容性；4.在小鼠身上进行毒性研究；5.在细胞培养中进行辐射增敏研究。DDFPe之前曾在人类身上进行过另一种应用的研究，但用于稳定乳剂的表面活性剂不是纯的。我们已经合成了用于稳定DDFPe的纯表面活性剂，这些表面活性剂应该是药学上可以接受的。实验的目的是测试和比较这些稳定DDFP的新型表面活性剂。从这些初步研究中，我们将确定用于正式临床前开发的DDFPe辐射增敏产品的原型。在第二阶段，我们将进行动物研究，其中我们将使用成像来显示治疗前后肿瘤缺氧的改善以及对低氧肿瘤的放射治疗改善肿瘤反应。与公共卫生相关：肿瘤缺氧在许多癌症中很常见，包括头颈癌、宫颈癌、前列腺癌和许多其他实体肿瘤。氧浓度低的肿瘤对放射治疗有抵抗力。这项美国国立卫生研究院第一阶段拨款申请旨在开发一种新的增敏剂，这种增敏剂可能比以前的化合物在改善缺氧癌细胞的氧合和改善癌症对治疗的反应方面更有效。