Imaging Tumor Blood Vessels in Bone Metastases

骨转移中的肿瘤血管成像

• 批准号: 6686187
• 负责人: WADIH ARAP
• 金额: $ 33.22万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-10 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6686187
• 关键词: angiogenesis; bioimaging /biomedical imaging; biomarker; bone marrow; breast neoplasms; clinical research; diagnosis design /evaluation; disease /disorder model; early diagnosis; human tissue; imaging /visualization /scanning; immunocytochemistry; intravital microscopy; laboratory mouse; metastasis; microcapsule; nanotechnology; neoplasm /cancer blood supply; neoplasm /cancer diagnosis; neoplastic process; peptide chemical synthesis; protein structure function; recombinant proteins; technology /technique development; vascular endothelium; xenotransplantation

DESCRIPTION (provided by applicant): We hypothesize that specific vascular addresses within tumor vasculature can be exploited for imaging and detection of metastatic breast carcinoma; our goal is to use these biochemical differences to develop targeted therapies. Here, we propose to investigate the molecular diversity of angiogenic vasculature during the tumor progression and metastases of breast cancer. Our specific aims are (i) to identify and characterize suitable markers of bone marrow metastases as targets for vascular imaging; (ii) to study the localization and distribution of the probes and respective receptors by imaging systems; (iii) to design, synthesize and validate devices for targeted imaging by developing novel tools for intravital imaging at the protein-protein level (such as engineered phage particles, recombinant proteins, nanoshells, or fluorescent microspheres). The most efficient targeting systems will be tested and validated in vivo in mouse models of bone marrow metastases. If successful, novel strategies to image metastatic breast cancer will be derived from this application. The approaches utilized in this application can be used to characterize the tumor microenvironment in breast cancer, changes and localization of receptors in the vascular endothelium of tumor blood vessels during breast cancer progression. In addition, probes that target breast cancer vasculature will be developed as delivery tools and will likely enhance effectiveness of current imaging technology.

描述（由申请人提供）： 我们假设肿瘤脉管系统内的特定血管地址可用于转移性乳腺癌的成像和检测；我们的目标是利用这些生化差异来开发靶向疗法。在这里，我们建议研究乳腺癌肿瘤进展和转移过程中血管生成脉管系统的分子多样性。我们的具体目标是（i）识别和表征合适的骨髓转移标志物作为血管成像的目标； (ii) 通过成像系统研究探针和各自受体的定位和分布； (iii) 通过开发蛋白质-蛋白质水平的活体成像新工具（例如工程噬菌体颗粒、重组蛋白、纳米壳或荧光微球）来设计、合成和验证用于靶向成像的装置。最有效的靶向系统将在小鼠骨髓转移模型中进行体内测试和验证。如果成功，转移性乳腺癌成像的新策略将从该应用中衍生出来。本申请中使用的方法可用于表征乳腺癌中的肿瘤微环境、乳腺癌进展期间肿瘤血管内皮中受体的变化和定位。此外，针对乳腺癌脉管系统的探针将被开发为递送工具，并可能增强当前成像技术的有效性。