新型Plectin-1荧光、MRI靶向分子探针对胰腺癌早期诊断的实验研究

项目名称： 新型Plectin-1荧光、MRI靶向分子探针对胰腺癌早期诊断的实验研究

项目编号： No.81471705

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： 王中秋

作者单位： 南京中医药大学

项目金额： 73万元

中文摘要： 分子影像使活体、早期发现肿瘤癌变过程中的分子异常成为可能。研究发现Plectin-1在胰腺癌及转移灶中高表达，在正常胰腺中不表达，表明Plectin-1与胰腺癌关系密切。本项目选择Plectin-1为成像靶点，首先构建荧光、纳米粒双模态靶向探针，采用透射电镜、X线电子衍射、振动样品磁强计、傅立叶红外等方法，对该探针进行性能检测；并将该探针和胰腺癌细胞PANC-1进行系列体外毒性试验和药代动力学试验，并和正常胰岛、成纤维细胞等对照；其次，将未标记和Plectin-1标记的探针注入胰腺癌鼠模型体内，进行活体荧光及MR显像；最后，使用HE染色、普鲁士蓝染色和Western印迹法等技术，检测离体标本肿瘤、瘤周组织的病理类型及探针分布状况，并与鼠模型的靶向成像结果进行对照分析。本研究通过Plectin-1靶向分子成像，活体、动态监测胰腺癌早期分子水平的异常，达到实现对胰腺癌早期诊断之目的。

中文关键词： 磁共振成像；分子影像；胰腺癌；plectin-1

英文摘要： Molecular imaging make the early detection of molecular abnormalities in the process of cancer possible in vivo. Recent studies display that Plectin-1 is overexpressed in human pancreatic cancer and metastasis,but undetectable in normal pancreas. The expression of Plectin-1 associated closely with pancreatic cancer, so we choose Plectin-1 for imaging targets. Firstly, we established dual-mode targeted probe with fluorescent and magnetic Nano-MR imaging (Cy5.5-anti- Plectin-1-PEG/SPIONs). The morphology and functions of the probe were tested by transmission electron microscope, X-ray diffraction, vibration magnetometer, Fourier transform infrared,et al.And the vitro toxicity and pharmacokinetic test were performed with pancreatic cancer cells PANC-1 ,as well as in normal islet cells and fibroblast for comparison. Secondly,the nontargeted and targeted molecular contrasts were injected intravenously into animal models of pancreatic cancer. Finally,we collected the specimen of tumors,surrounding tissues and other major organs,and detected the pathological types and distribution of probe arroud cells by HE dyeing, Prussian blue staining and Western blotting, and then, the results of targeted enhancement in animal models of pancreatic cancer were compared.The research aims to achieve early diagnosis at the molecular level in pancreatic cancer,which is based on the Plectin-1 targeted molecular imaging in vivo, dynamic monitoring molecular abnormalities of pancreatic cancer.

英文关键词： MRI;Molecular imaging;Pancreatic cancer;Plectin-1