Design and Evaluation of Hypoxia Enhanced Bombesin Analogs for Prostate Cancer

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DESCRIPTION (provided by applicant): Career Goals: My immediate goals are to obtain the required training to become a translational research capable of developing diagnostic/therapeutic cancer agents for clinical trials. My long-term goals are to becoming an independent research scientist at an academic medical center specializing in cancer research. Research Project: Our proposal is to enhance the efficacy of diagnostic radiopharmaceuticals for the detection of prostate cancer by incorporating hypoxia trapping agents into the structure of tumor specific targeted peptides. We propose to test our theory by incorporating nitroimidazoles (hypoxia trapping agents) into the structure of the Bombesin (BBN) peptide. The proposed 1111n-BBN analogs are expected to exhibit increased residence time of the diagnostic agent in prostate tumors. The increase in retention time in the hypoxic sections of the tumor will provide significantly enhanced diagnostic images by yielding higher tumor to non-target ratios. If successful, this technology could drastically enhance the efficacy of BBN and other tumor specific targeted small molecules, peptides and antibodies. Career Development: The mentorship team in this application is designed to educate the applicant in the necessary skill set to become a translational cancer researcher. The basic and preclinical laboratory training will be provided by the mentor (Hoffman) and co-mentor (Volkert). The co-mentor (Perry) will provide the applicant with a clinical perspective on radiopharmaceutical development and how it relates to patient care. The formal training program will include a combination of didactic lectures, attendance at seminar presentations, practical training in the use of mouse models and oncology, practical training in the use of molecular and anatomic imaging techniques. Environment: The applicant will have access to Dr. Hoffman's laboratory (2,600 sq.ft.) fully equipped for the proposed synthesis and evaluation of the hypoxia enhanced Bombesin analogs. Also, the applicant will have access to the VA Animal Research Facility, Biomolecular Imaging Center, VA Nuclear Medicine Service, MU Cell and Immunobiology Core Facility and the MU Structural Biology Core. RELEVANCE: Currently in the United States, prostate cancer is the second leading cause of cancer related death in men. The diagnostic radiopharmaceuticals we will develop and evaluate will provide clinicians a crucial tool in the detection and staging of prostate cancer. The technology developed in this proposal may significantly increase the efficacy of diagnostic and therapeutic drugs in prostate and other forms of cancer.