脑胶质瘤新型靶点- - TEM8受体高选择性双模态多肽分子探针的筛选构建及活体成像研究

项目名称： 脑胶质瘤新型靶点- - TEM8受体高选择性双模态多肽分子探针的筛选构建及活体成像研究

项目编号： No.81201132

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 权启萌

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： TEM8受体与肿瘤新生血管密切相关，是一种新型优越的评估肿瘤血管化程度的标记，逐渐成为国际肿瘤分子影像学研究的希望。将TEM8做为靶标研发多肽、融合蛋白等进行抗肿瘤血管化治疗在国际上有一定报道。申请人也在国际上首次合成18F-FP-QQM多肽分子探针可视化肿瘤TEM8蛋白表达水平。脑胶质瘤在中枢神经系统肿瘤中侵袭性最高，其早期诊断及治疗是临床研究难点，我们前期实验结果显示C6胶质母细胞瘤细胞高表达TEM8蛋白。 因此，本项目拟以QQM多肽为基础展开双重噬菌体展示，筛选易于透过血脑屏障的靶向脑胶质瘤TEM8受体的更高特异性多肽序列，兼具器官及分子特异性，并构建多肽靶向的双模态成像分子探针，通过MR及光学成像获得原位接种U87模型TEM8受体生物学特征的可视化数据，整合分析，实现无创，动态，定量分析TEM8相关的脑胶质瘤发展，为早期诊断，动态监控病情提供新方法，为合理治疗并评估疗效提供新思路。

中文关键词： 肿瘤内皮细胞受体8；多肽；脑胶质瘤；双模态成像；肿瘤靶向

英文摘要： The upregulation of tumor endothelial marker 8 (TEM8) on the endothelial cells of blood vessels has been proved highly related to tumor angiogenesis, making this receptor a particularly superior new candidate for future tumor angiogenesis targeting studies. Several antiangiogenesis studies have been conducted based on the interaction between the ligand (such as peptides, fusion protein) and the TEM8 receptor. The applicant had reported a molecular tracer of 18F-FP-QQM that was the first time that TEM8 expression has been visualized with PET using a peptidic probe. Glioma showed highly infiltrative properties in the central nervous system tumors. There is an urgent clinical need for its early diagnosis and treatment. Our preliminary data showed a high expression of TEM8 on C6 glioblastoma cell line. Therefore, we are going to perform parallel in vitro and in vivo selection using phage display to identify peptides that accumulate within tumors in vivo and target to the TEM8 receptor on glioma. By comparing to structure of QQM, we aim to develop a newly, highly selective targeting peptide sequence, that easily go across the brain blood barrier. This binding peptide has both organ-specific and molecular-specific properties. Furthermore, we would develop a dual-modality tumor objective targeting nanoparticles with bo

英文关键词： Tumor Endothelial Marker (TEM8)；QQM peptide；Glioma；Dual-functional imaging; Tumor targeting；Tumor targeting