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

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.