基于EGFR靶向的PET/荧光肿瘤分子成像研究

项目名称： 基于EGFR靶向的PET/荧光肿瘤分子成像研究

项目编号： No.21501020

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 环境科学、安全科学

项目作者： 焦扬

作者单位： 大连理工大学

项目金额： 20万元

中文摘要： 表皮生长因子受体（EGFR）的信号转导和许多癌症前病变和恶性肿瘤有关，研究可以识别EGFR的分子探针对于癌症的早期诊断以及研究肿瘤的形成机理都具有十分重要的意义。本项目设计Off-On开关式分子靶向荧光探针，用市场中技术成熟的靶向药物的分子骨架作为识别基团，通过具有良好水溶性的链接基团与具有较高荧光量子产率的荧光基团相连，在EGFR分子靶向药物的分子骨架结构中引入18F标记，得到在复杂生命体系中特异性识别EGFR的PET/荧光双信号响应分子探针，探针具有良好靶向性、高灵敏度和生物兼容性。基于分子内光诱导电子转移原理，探针未与EGFR靶向结合时，呈现折叠状态，荧光为off状态，降低背景荧光，探针结合EGFR靶向后识别基团与靶点作用于细胞的内表面，折叠构象伸展，使得探针荧光恢复，点亮肿瘤细胞。识别基团为成药的有效部分，同时兼具治疗作用，实现诊疗一体。

中文关键词： 表皮生长因子受体；荧光；肿瘤分子

英文摘要： The signal transduction networks of epidermal growth factor receptor (EGFR) was considered that associate with many former cancer lesionsand malignant tumors, and the research on molecular probes of EGFR make great significance in/play a important role in the diagnosis of cancer and the formation mechanism of early cancer. This project is based on the design of Off-On switch mode molecular targeted fluorescent probes. These probes include three parts which are recognition groups, connected groups and fluorescenc groups. Firstly, the mature EGFR targeted drugs are used to be recognition groups which could purchase from markets directly. The second, link groups which have good water solubility will be choosed. The third, the fluorescence groups should have highly fluorescence quantum yield rate. The fluorescence groups and recognition groups are connected with link groups. 18F labeled is introduced into the molecular backbone structure of the EGFR molecular targeted drugs, and 18F-labeled probes can be achieved PET scan imaging to get the corresponding probemolecule which having dual targeting and good biocompatibility. According to intramolecular photoinduced electron transfer theory, the fluorescence is off state when the probe is not combined with targeting EGFR, and the probes are showing the folded state. However, when the probe is combined with targeting EGFR, the fluorescence is on, and the probes are showing the enhanced state. The recognition groups are valid part of the medicine, so that the probe has both recognition and therapeutic effect, can realize to diagnosis and treatment at the same time.

英文关键词： EGFR;fluorescence;tumor molecular