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: 8232144
• 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 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8232144
• 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; Instruction; 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

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.

职业目标：我的近期目标是获得必要的培训，成为一名翻译研究人员。 能够开发用于临床试验的诊断/治疗癌症剂。我的长期目标是 成为一个独立的研究科学家在学术医学中心专门从事癌症研究。 研究项目：我们的建议是提高诊断放射性药物的疗效， 通过将缺氧捕获剂掺入肿瘤特异性结构中检测前列腺癌 靶向肽。我们建议将硝基咪唑（缺氧捕获剂） 蛙皮素（BBN）肽的结构。预期所提出的1111 n-BBN类似物表现出 增加诊断剂在前列腺肿瘤中的停留时间。保留时间的增加， 肿瘤的低氧切片将通过产生更高的肿瘤体积而提供显著增强的诊断图像。 非目标比例。如果成功，这项技术可以大大提高BBN和其他药物的疗效。 肿瘤特异性靶向小分子、肽和抗体。 职业发展：本申请中的导师团队旨在教育申请人 成为一名转化型癌症研究人员所需的技能。基础和临床前实验室 培训将由指导者（霍夫曼）和共同指导者（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 病人护理正式的培训计划将包括教学讲座，出席 研讨会演讲，小鼠模型和肿瘤学使用的实践培训， 使用分子和解剖成像技术。 环境：申请人可以使用霍夫曼博士的实验室（2，600平方英尺）齐全的 所提出的缺氧增强蛙皮素类似物的合成和评价。此外，申请人将 可以访问VA动物研究机构，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。

项目成果

Synthesis and in vitro and in vivo evaluation of hypoxia-enhanced 111In-bombesin conjugates for prostate cancer imaging.

用于前列腺癌成像的缺氧增强 111In-铃蟾肽缀合物的合成及体外和体内评估。

• DOI: 10.2967/jnumed.112.117986
• 发表时间: 2013-09
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: Zhou Z;Wagh NK;Ogbomo SM;Shi W;Jia Y;Brusnahan SK;Garrison JC
• 通讯作者: Garrison JC