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：我目前的目标是接受必要的培训，成为一名翻译研究人员 能够开发用于临床试验的诊断/治疗癌症药物。我的长期目标是 成为一家专门从事癌症研究的学术医学中心的独立研究科学家。 研究项目：我们的建议是提高诊断放射性药物对癌症的疗效 肿瘤特异性结构掺入低氧捕捉剂检测前列腺癌 靶向多肽。我们建议通过加入硝基咪唑(低氧捕捉剂)来检验我们的理论。 进入BBN(BBN)肽的结构。拟议的1111N-BBN类似物预计将展示 诊断试剂在前列腺癌中的停留时间增加。中保留时间的增加 肿瘤的低氧切片将通过产生更高的肿瘤来提供显著增强的诊断图像。 对非目标比率。如果成功，这项技术可以极大地提高BBN和其他 肿瘤特异性靶向小分子、多肽和抗体。 职业发展：此申请表中的指导团队旨在教育申请者 成为一名翻译癌症研究人员的必备技能。基础实验室和临床前实验室 培训将由导师(霍夫曼)和共同导师(沃尔克特)提供。联合导师(佩里)将 为申请人提供放射性药物开发的临床观点及其与 病人护理。正式的培训计划将包括授课讲座、出席 研讨会报告、使用老鼠模型和肿瘤学的实践培训、 分子和解剖成像技术的使用。 环境：申请人可以进入霍夫曼博士的实验室(2600平方英尺)。配备齐全的 低氧增强蛙黄素类似物的合成和评价。此外，申请者将 可以使用退伍军人事务部动物研究设施、生物分子成像中心、退伍军人事务部核医学中心 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