靶向EphB4的放射性分子探针在体诊治评价

项目名称： 靶向EphB4的放射性分子探针在体诊治评价

项目编号： No.81471708

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 宋少莉

作者单位： 上海交通大学

项目金额： 73万元

中文摘要： 靶向受体酪氨酸激酶对肿瘤的诊治仍是研究的热点。Eph受体家族及其配体Ephrin是目前已知的酪氨酸蛋白激酶受体家族中最大的一个亚家族，EphB4在肿瘤血管形成、肿瘤的转移、侵袭中发挥着重要作用。靶向EphB4对肿瘤进行诊治，已成为热点。已有多种靶向EphB4的药物研制成功。但不同肿瘤EphB4的表达量不同，迫切需要活体监测肿瘤EphB4的表达，及时反应肿瘤治疗后的变化。课题组一直致力于靶向EphB4家族的研究，已研制出靶向EphB4的小分子多肽TNYL-RAW，具有高度EphB4靶向性，人源性单克隆抗体hAb131对EphB4也有高度靶向性。188Re具有优良γ和β特性，适用于体内治疗和显像，因此本课题拟利用188Re标记靶向EphB4的小分子探针TNYL-RAW和单抗hAb131，研制出靶向肿瘤EphB4的放射免疫治疗及显像分子探针，用于肿瘤的治疗及体内可视化研究。预实验证实该方法可行。

中文关键词： 分子影像探针；肿瘤靶向；靶向治疗；分子影像

英文摘要： Targeting receptor tyrosine kinases (RTKs) in cancer diagnosis and treatment is still the main focus in many anticancer research. Eph receptors (Ephs) are the largest subfamily of receptor tyrosine kinases. Eph receptor tyrosine kinases and their ephrin ligands are involved in various signalling pathways and mediate critical steps of a wide variety of physiological and pathological processes. Increasing experimental evidence demonstrates that both Eph receptor and ephrin ligands are overexpressed in a number of human tumours, and are associated with tumour growth, invasiveness and metastasis. EphB4 kinases plays key roles in the development of the tumor develop and matastis. Increasing evidence showed that over express EphB4 is a predict for colorectal cancer who may not response to Avastin. In this regard, targeting EphB4 for anticancer therapies for EphB4 over express tumours is of great potential for anticancer research. Our research group had developed a small molecule peptide named TNYL-RAW, which has a high specifity that targeting EphB4. Human monoclonal antibody hAb131 also has highly specifity to EphB4. Radio isotope 188Re has an excellent characteristics for in vivo therapeutic and imaging. In this regard, we use 188Re labeled small molecular probes TNYL-RAW and humanized antibody hAb131 targeting EphB4. Aim at developed a radioimmunotherapy agents targeting tumor over expressed EphB4. Preliminary experiments confirmed that this concept is feasible.

英文关键词： molecular probe;tumor target;target therapy;molecular imaging