多功能稀土纳米探针用于VX2瘤靶向性CT造影剂和放疗增敏剂的影像学研究

项目名称： 多功能稀土纳米探针用于VX2瘤靶向性CT造影剂和放疗增敏剂的影像学研究

项目编号： No.81471714

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： 左长京

作者单位： 中国人民解放军第二军医大学

项目金额： 70万元

中文摘要： 目前CT造影剂的主成分碘，存在对X射线衰减不强、一定的肾毒性、血半衰期短等不足。新型稀土纳米探针BaYbF5:2%Tm3+中重金属元素镱、钡的X射线衰减系数高于碘，血半衰期较长有利于EPR效应被动富集，还可连接靶向配体主动靶向富集，且稀土重金属纳米颗粒具有放疗增敏效应。据此，本项目拟建立肺VX2瘤大型哺乳动物深部脏器肿瘤模型为研究平台， RGD修饰靶向探针组与非靶向探针组CT扫描比较，观测CT造影剂效果、主动靶向效果； 比较对照组、单纯放疗组、非靶向探针+放疗组、靶向探针+放疗组的差别，判断靶向探针的放疗增敏效果。CT观测造影剂强化效果、肿瘤大小， FDG PET/CT测量肿瘤代谢变化，检测血VX2瘤标志物特异性DNA量的变化。病理测量肿瘤大小、瘤细胞坏死率、EGFR、凋亡率、细胞周期、重要脏器有无损伤。以病理和CT测量值为金标准，统计分析和评价。为多功能稀土纳米探针的优化及应用奠定基础。

中文关键词： 稀土纳米探针；对比剂；体层摄影术；X线计算机；VX2瘤；放射治疗

英文摘要： Iodine ions in Iodinated contrast agent for CT has shortcomings such as weak X-ray attenuation, renal toxicity, and short plasma half-life. BaYbF5:2%Tm3+ is a newtype rare earth nanoprobe, which contains heavy metals such as Ba and Yb with higher X-ray attenuation coefficient and longer plasma half-life. It means that this newtype nanaprobe could be passive enriched in solid VX2 tumor because of enhanced permeability and retention (EPR) effect, targeting ligands also could be linked on the probe for active targeting enriched in VX2 tumor. Moreover, the heavy metal nanoparticles is a kind of radiosensitizer. Hereby, we will establish a rabbit lung VX2 tumor model as the research platform, rabbits in non-targeted nanoprobe group and RGD peptide modified targeted nanoprobe group were performed CT scan to evaluate the CT enhancement and active targeted effect in the tumor between two groups. Those rabbits also underwent radiotherapy and the radiosensitization of targeted nanoprobe were evaluated by comparing with radiotherapy only group and control group. CT enhancement effect, tumor size, and metabolic change of the tumor pre- and post radiotherapy were measured on enhanced CT and PET/CT, respectively. All rabbits were sacrificed, the tumor volume, tumor cell necrosis rate, EGFR, apoptosis rate, tumor cell cycle were tested and measured. Organs such as heart, kidney, liver were examined whether with damage or not. All analysis were taken pathology results and CT measurements as gold standard. This study will lay the foundation for the optimization and clinical application of the multifunctional rare-earth nanoprobe.

英文关键词： rare-earth nanoprobe;contrast agent;tomography;X-ray computed;VX2 tumor;radiotherapy