HER2亲和体-凋亡素靶向诊断与治疗分子探针的构建及其在乳腺癌中的应用研究

项目名称： HER2亲和体-凋亡素靶向诊断与治疗分子探针的构建及其在乳腺癌中的应用研究

项目编号： No.81471710

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： 段小艺

作者单位： 西安交通大学

项目金额： 70万元

中文摘要： 基于分子成像技术开发兼具诊断与治疗作用的新型分子探针将有可能改变现有恶性肿瘤的诊疗模式。既往实验发现，针对肿瘤表皮生长因子受体-2（HER2）抗原表位设计的短肽适合于靶向成像，凋亡素能选择性诱导肿瘤细胞凋亡。基于此，本课题拟以HER2阳性乳腺癌作为研究对象，以与乳腺癌发生、转归密切相关的HER2作为靶点，以凋亡素作为治疗因子，采用模拟肽表位基因串联技术、基因工程技术、正电子核素标记技术等，设计并构建18F标记的HER2亲和体-凋亡素融合肽，希望其成为兼具诊断与治疗作用的双功能靶向分子探针。通过离体实验评估此探针与靶细胞结合、进入细胞以及诱导选择性杀伤肿瘤细胞的能力，在体PET成像了解探针在动物体内分布与代谢特征，评价其针对HER2阳性乳腺癌荷瘤动物靶向成像与治疗效果。本课题的实施旨在为新型分子探针的开发与应用提供实验依据，为乳腺癌特异性诊断与指导个体化治疗开辟新的途径。

中文关键词： 分子影像；分子探针；乳腺癌；肿瘤靶向

英文摘要： The pattern of diagnosing and treating malignant tumor will be significantly altered due to the development of dual function molecular imaging which provide not only accurate diagnosis but also early intervention. Our previous research revealed that tumor-targeted imaging can be achieved via the short peptide against the human epidermal growth factor receptor type 2(HER2), and apoptin is effective in the tumor selected apoptosis. Based on these findings, we will employ HER2 targeting molecules and apoptin to develop dual function probe for the targeted diagnosis and treatment for HER2-positive breast cancer. For this purpose, mimetic peptide epitope gene tandem technique, genetic engineering and nuclide labeled techniques will be combined to construct 18F labeled HER2 affibody-apoptin fusion peptide. Its targeted binding, entering cell and selective tumor cell killing capability will be evaluated in vitro. Furthermore, its distribution and metabolism will be observed in vivo with micro-PET technique. Tumor-burdened animal model will be established to investigate the targeted imaging and molecular treating of the probe. We hope the successful completion of this project will offer experimental evidence for the application of novel molecular probe and may open a new avenue to the targeted diagnosis and individualized therapy for breast cancer.

英文关键词： molecular imaging;molecular probe;breast cancer;tumor targeting