Design and Evaluation of Hypoxia Enhanced Bombesin Analogs for Prostate Cancer

缺氧增强铃蟾肽类似物治疗前列腺癌的设计和评价

• 批准号: 8033262
• 负责人: Jered C Garrison
• 金额: $ 24.15万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8033262
• 关键词: 90Y; Academic Medical Centers; Affinity; Anatomy; Binding; Bombesin; Cancer Etiology; Cancer Model; Cells; Cessation of life; Clinical; Clinical Trials; Core Facility; Detection; Development; Diagnostic; Diagnostic Imaging; Discipline of Nuclear Medicine; Drug Kinetics; Environment; Evaluation; Exhibits; Goals; Hypoxia; ICAM1 gene; Image; Imaging Techniques; Immunobiology; In Vitro; Label; Laboratories; Laboratory Animal Production and Facilities; Malignant Neoplasms; Malignant neoplasm of prostate; Mentors; Mentorship; Molecular; Nitroimidazoles; Patient Care; Peptide antibodies; Peptides; Pharmaceutical Preparations; Pilot Projects; Property; Prostate; Prostatic Neoplasms; Radiopharmaceuticals; Research; Research Personnel; Research Project Grants; Scientist; Services; Staging; Structure; Technology; Testing; Therapeutic; Time; Training; Training Programs; Translational Research; United States; X-Ray Computed Tomography; analog; anticancer research; career; career development; design; in vivo; lectures; men; molecular imaging; mouse model; oncology; pre-clinical; receptor; residence; single photon emission computed tomography; skills; small molecule; square foot; structural biology; theories; tool; tumor; vector

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.

描述（由申请人提供）：职业目标：我的近期目标是获得所需的培训，成为一个翻译研究能够开发诊断/治疗癌症药物的临床试验。我的长期目标是成为一名独立的研究科学家，在一个专门从事癌症研究的学术医疗中心。 研究项目：我们的建议是通过将缺氧捕获剂掺入肿瘤特异性靶向肽的结构中来增强诊断放射性药物用于检测前列腺癌的功效。我们建议通过将硝基咪唑（缺氧捕获剂）纳入蛙皮素（BBN）肽的结构来测试我们的理论。预期所提出的1111 n-BBN类似物在前列腺肿瘤中表现出诊断剂的增加的停留时间。在肿瘤的缺氧切片中的保留时间的增加将通过产生更高的肿瘤与非靶比来提供显著增强的诊断图像。如果成功，这项技术可以大大提高BBN和其他肿瘤特异性靶向小分子、肽和抗体的疗效。 职业发展：本申请中的导师团队旨在教育申请人成为转化癌症研究人员所需的技能。基础和临床前实验室培训将由导师（霍夫曼）和共同导师（Hoffert）提供。共同导师（佩里）将为申请人提供放射性药物开发的临床观点，以及它与患者护理的关系。正式的培训计划将包括教学讲座，出席研讨会演讲，使用小鼠模型和肿瘤学的实践培训，使用分子和解剖成像技术的实践培训。 环境：申请人可以使用霍夫曼博士的实验室（2，600平方英尺）完全装备用于所提出的低氧增强蛙皮素类似物的合成和评价。此外，申请人将有权使用VA动物研究设施，生物分子成像中心，VA核医学服务，MU细胞和免疫生物学核心设施和MU结构生物学核心。