人肺腺癌脑转移动物模型建立及显像的研究  

An Experimental Study on the Chinese Lung Adenocarcinoma Cell Clone CPA-Yang1-BR with Brain Metastasis Potency in Nude Mice and In Vivo Imaging Research

作　　者：雷贝[1] 曹杰[1] 沈杰[2] 赵兰香[3] 梁胜[4] 孟庆刚[5] 谢文晖[1] 杨顺芳[1] 

机构地区：[1]上海交通大学附属胸科医院核医学科,上海200030 [2]复旦大学附属上海市公共卫生中心放射科,上海201508 [3]上海交通大学附属胸科医院病理科,上海200030 [4]上海交通大学附属瑞金医院核医学科,上海200025 [5]复旦大学药学院,上海201210

出　　处：《中国肺癌杂志》2013年第8期391-399,共9页Chinese Journal of Lung Cancer

基　　金：上海市科学技术委员会创新行动计划实验动物项目(No.09140901500)资助~~

摘　　要：背景与目的肺癌脑转移是临床常见的严重并发症,由于脑部结构和功能的特殊性、脑转移检测方法的局限性,预后很差。本研究旨在筛选人肺腺癌脑转移细胞株CPA-Yang1-BR以及建立裸小鼠动物模型和检测方法。方法将人肺腺癌细胞株CPA-Yang1-GFP接种于裸小鼠左心室,约7周-8周后比较三种小动物显像方法:microPET/CT显像,X线、放射性核素、荧光(三合一)活体成像系统和小动物线圈MRI显像,实验证明MRI显像是最准确的小鼠脑转移病灶检测方法。脑核磁共振成像(magnaticresonanceimaging,MRI)显像找到脑转移灶,深麻醉处死裸小鼠取出脑转移病灶,部分病理验证,部分行原代培养后获得人肺腺癌脑转移细胞,再次接种裸小鼠,用上述方法重复以上体内外循环4次,观察脑转移形成情况。结果获得人肺腺癌脑转移细胞株CPA-Yang1-BR及其裸小鼠模型。结论 CPA-Yang1细胞经反复裸小鼠脑组织内外筛选的方法可获得具有高转移潜能的裸小鼠脑转移模型,为肺癌脑转移的生物学研究提供了一个良好的技术平台。小动物线圈MRI或microMRI活体显像是检测小鼠肺癌脑转移敏感、准确、无创伤的显像方法。Background and objective Lung cancer is the leading cause of cancer-related death in men and wom- en. It is also the most common cause of brain metastases. A brain metastasis model is difficult to be established because of the presence of the blood-brain barrier （BBB） and the lack of optimal methods for detecting brain metastasis in nude mice. Thus, the establishment of a Chinese lung adenocarcinoma cell line and its animal model with brain metastasis potency and in vivo research is of great significance. Methods CPA-Yangl cells were obtained from a patient with human lung adeno- carcinoma by lentiviral vector-mediated transfection of green fluorescence protein. Intracardiac inoculation of the cells was performed in nude mice, and brain metastatic lesions were detected using micro ~SF FDG-PET/CT scanners, small animal in vivo imaging system for fluorescence, radionuclide and X ray fused imaging, magnetic resonance imaging （MR/） with sense body detection, and resection. The samples were divided into two parts for cell culture and histological diagnosis. The process was repeated in vivo and in vitro for four cycles to obtain a novel cell done, CPA-Yangl-BR. Results A novel cell clone, CPA-Yangl-BR, was obtained with a brain metastatic rate of 50%. The use of MR/for the detection of brain metasta- ses has obvious advantages. Conclusion An experimental Chinese lung adenocarcinoma cell clone （CPA-Yangl-BR） and its animal model with brain metastasis potency in nude mice were established. MRI with sense body or micro MR/may be used as a sensitive, accurate, and noninvasive method to detect experimental brain metastases in intact live immunodeficient mice. The results of this study may serve as a technical platform for brain metastases from lung adenocarcinoma.

关 键 词：肺肿瘤 肿瘤转移 脑 动物模型 PET MRI 

分 类 号：R734.2[医药卫生—肿瘤]