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靶向纳米探针，以实现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。它汇集了三个研究小组，在血管生成和癌症小鼠模型（Hanahan，UCSF），血管分析（Ruoslahti，Burnham研究所）以及临床和实验分子成像（Franc，UCSF）方面具有互补的专业知识。已经发现肽通过循环系统特异性地归巢到高级别瘤形成和/或浸润性癌的血管生成血液或淋巴新血管系统。这些血管特征可以将癌性病变与其同源正常组织以及与其他器官和肿瘤状况中的血管/淋巴管区分开。其目标是： 1.开发成像纳米探针，用于检测两种逐步进展为癌症的癌症小鼠模型中的血液和淋巴管新生血管，使用经验证的特征发现肽作为与适用于SPECT、PET或MRI成像的试剂连接的模块化特异性元件。 2.发现和表征宫颈和胰腺导管肿瘤和癌症的血液和淋巴管系统的新特征发现肽的库，并确定哪些识别同源人类疾病中的类似病变。 3.竞争性评价来自目标2的小鼠/人特征发现肽（及其混合物），以确定在宫颈癌（作为原型）和胰腺导管癌（其未满足的临床需求）小鼠模型中将成像报告分子递送至异常血液和淋巴管的最佳方案。 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，该小鼠模型由与这些中心正在开发的新成像纳米结构连接的最佳人/小鼠特征识别肽组成，以确定用于临床评估的最佳候选纳米探针。 通过将成像剂递送到肿瘤血管生成和淋巴管生成的器官部位，待开发的模块化成像纳米探针有望实现人类癌症的早期检测。

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.