Detecting cancer early with targeted nano-probes for va*

描述(由申请人提供)： 该项目将开发用于分子成像的有针对性的纳米探针，以实现对早期癌症的非侵入性早期检测，从而在灵敏度和选择性方面提供实质性改进。它汇集了三个在血管生成和癌症小鼠模型(哈纳汉，加州大学旧金山分校)、血管成像(鲁斯拉夫蒂，伯纳姆研究所)以及临床和实验分子成像(弗朗克，加州大学旧金山分校)方面具有互补专业知识的研究小组。已发现多肽通过循环系统特异性地进入高级别肿瘤和/或浸润性癌的血管新生血管或淋巴管新生血管。这些血管特征可以区分癌病变与其同源正常组织，以及与其他器官和肿瘤情况下的血管/淋巴管。目标是： 1.开发成像纳米探针，用于检测两种逐步进展为癌症的小鼠模型中的血液和淋巴管新生血管，使用经过验证的特征发现多肽作为模块特异性元件，连接到适合于SPECT、PET或MRI成像的试剂。 2.发现和鉴定宫颈和胰腺导管肿瘤和癌症的血液和淋巴管系统的新的特征发现多肽，并确定在同类人类疾病中识别相似病变的多肽。 3.竞争性评估Aim 2中的鼠/人特征识别多肽(及其混合物)，以确定在向宫颈癌(作为原型)和胰腺癌(其临床需求尚未得到满足)模型的小鼠的异常血液和淋巴管输送成像报告方面最好的。 4.与癌症纳米技术卓越中心合作，在小鼠模型中测试纳米探针，该模型由与这些中心正在开发的新成像纳米结构相联系的最佳人/鼠签名寻找多肽组成，以确定用于临床评估的最佳候选纳米探针。 将开发的模块化成像纳米探针，通过将成像试剂输送到肿瘤血管生成和淋巴管生成的器官部位，有望使人类癌症的早期检测成为可能。

DESCRIPTION (provided by applicant): This project will develop targeted nano-probes for molecular imaging to enable non-invasive early detection of incipient cancer, affording substantive improvements in sensitivity and selectivity. It brings together three research groups with complementary expertise in angiogenesis and mouse models of cancer (Hanahan, UCSF), in vascular profiling (Ruoslahti, Burnham Institute), and in clinical and experimental molecular imaging (Franc, UCSF). Peptides have been discovered that specifically home through the circulatory system to the angiogenic blood or lymphatic neo-vasculature of high-grade neoplasias and/or invasive carcinomas. These vascular signatures can distinguish cancerous lesions from their cognate normal tissue, as well as from blood/lymphatic vessels in other organs and neoplastic conditions. The aims are: 1. Develop imaging nanoprobes for detecting the blood and lymphatic neo-vasculature in two mouse models of cancer that undergo stepwise progression to carcinoma, using validated signature-finding peptides as modular specificity elements linked to agents appropriate for imaging with SPECT, PET, or MRI. 2. Discover and characterize a repertoire of new signature-finding peptides for blood and lymphatic vasculature of cervical and pancreatic ductal neoplasias and cancer, and determine which identify analogous lesions in the cognate human diseases. 3. Competitively evaluate mouse/human signature-finding peptides (and mixtures thereof) from Aim 2 to identify the best at delivering imaging reporters to the aberrant blood and lymphatic vasculatures in the mouse models of cervical (as a prototype) and pancreatic ductal cancer (for its an unmet clinical need). 4. In partnership with Centers of Excellence in Cancer Nanotechnology, test nano-probes in the mouse models consisting of the best human/mouse signature-finding peptides linked to new imaging nanostructures being developed by those centers, to identify optimal candidate nanoprobes for clinical evaluation. The modular imaging nanoprobes to be developed, by delivering imaging agents to organ sites of tumor angiogenesis and lymphangiogenesis, hold promise to enable early detection of human cancer.