Imaging Tumor Blood Vessels in Bone Metastases from Breast Cancer

描述(由申请人提供)： 我们假设肿瘤血管中的特定血管地址可以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有针对性的治疗方法。在这里，我们建议研究血管新生血管在乳腺癌进展和转移过程中的分子多样性。我们的具体目标是(I)确定和表征合适的骨髓转移标记物作为血管成像的靶标；(Ii)研究成像系统中探针和相应受体的定位和分布；(Iii)通过开发蛋白质-蛋白质水平的活体成像的新工具(如工程噬菌体颗粒、重组蛋白、纳米壳或荧光微球)来设计、合成和验证靶向成像设备。最有效的靶向系统将在体内对骨髓转移的小鼠模型进行测试和验证。如果成功，将从这一应用中衍生出成像转移性乳腺癌的新策略。该方法可用于表征乳腺癌的肿瘤微环境、肿瘤血管内皮细胞受体在乳腺癌进展过程中的变化和定位。此外，针对乳腺癌血管的探针将被开发为输送工具，并可能增强当前成像技术的有效性。

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.