荧光-钆双模态MR靶向对比剂对微小肿瘤VEGFR-2受体精准定位显像的实验研究

项目名称： 荧光-钆双模态MR靶向对比剂对微小肿瘤VEGFR-2受体精准定位显像的实验研究

项目编号： No.81460262

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 涂蓉

作者单位： 海南医学院

项目金额： 47万元

中文摘要： 精准医学是分子影像学的发展方向，光学与结构多模融合成像能提高成像质量。经我们前期系列研究发现，肿瘤新生血管及肿瘤细胞膜上的VEGFR-2受体是一种理想的分子靶点，对其进行荧光-MR双模态靶向成像，有望实现肿瘤的精准定位和定量诊断。 本研究将荧光VEGF拮抗小肽(VEGF127-133)与钆（Gd）连接到聚赖氨酸树枝大分子表面，构建一种新型MR靶向对比剂，其粒径只有我们前期抗体实验的1/80(5nm)。通过体外细胞学实验、荷瘤动物活体内荧光成像、MR成像、病理及毒理学实验观察；从分子、细胞、组织和器官水平分析该对比剂肿瘤精准定位和定量的性能、吸收、组织分布、代谢规律及急性毒性情况，探讨其成像机制，为新型肿瘤MR靶向对比剂设计奠定实验基础。本研究在肿瘤靶点、对比剂的运载体和显像剂三个方面都实现了在前期实验基础上的新突破。

中文关键词： 荧光；VEGF小肽；钆；双模态靶向对比剂；肿瘤诊断

英文摘要： Precision Medicine is a new direction of molecular imaging because it combines both the optical and structural multimode fusion imaging that can significantly improve the imaging quality. Our previous study established that VEGFR-2 receptor of tumor cells and growing vessels is a prospective molecular target. Fluorescence-MR double mode targeted imaging on VEGFR-2 has a great potential for precise positioning and quantitative diagnosis of tumor. This study aims to construct a new MR targeting agent by combining the fluorescent VEGF127-133 and gadolinium (Gd) with the polylysine dendrimer surface. The particle size of the new agent is designed only about the 1/80 (5nm) of that used in our previous antibody study. Through a series of experiments, including an in-vitro cell experiment, in vivo fluorescence imaging, MR imaging, and pathology and toxicology experiments on knockout models, the tumor precise positioning and quantitative ability, absorption, distribution and metabolism, and as well as acute toxicity of the agent will be analyzed at the molecular, cellular, and tissue and organ levels. The imaging mechanism by which the new MR tumor targeting agent is designed will also be studied. This study is expected to generate new breakthroughs in three aspects of tumor targeting, agent carrier and MR targeting agent.

英文关键词： Fluorescent;VEGF peptide;Gd;bimodal targeted MR contras;diangnosis of tumor