肺腺癌脑转移动物模型的生物发光成像和SPECT/CT的比较  

Comparison between bioluminescence imaging and SPECT/CT of mouse models of brain metastasis from lung adenocarcinoma

作　　者：陈愉生[1,2,3] 陈正伟[1,2] 俞梅娥 涂洵崴 李鸿茹[1,2,3] 林凌[4] 林如辉[5] 

机构地区：[1]福建医科大学省立临床医学院 [2]福建省立医院呼吸内科,福州350000 [3]福建省呼吸四病研究室,福州350000 [4]福建医科大学基础医学院,福州350000 [5]福建中医药大学中西医结合研究院,福州350000

出　　处：《中国实验动物学报》2017年第1期36-42,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家卫生计生委科研基金-福建省卫生教育联合攻关计划项目(WKJ-FJ-17);福建省立医院优秀青年医师项目(2014YNQN03);福建省自然科学基金(2015J01376)

摘　　要：目的利用稳定表达荧光素酶的luc+-PC-9人肺腺癌细胞建立肺癌脑转移动物模型,比较生物发光成像和18F-FDG(18F-fluorodeoxyglucose,18F-氟代脱氧葡糖)SPECT/CT在肺癌转移模型中的评估作用。方法将luc+-PC-9细胞悬液经左心室注入BALB/c裸鼠建立肺癌脑转移模型,分别在第4、5周行生物发光成像、^(18)F-FDG SPECT/CT检查观察裸鼠成瘤情况,以H&E染色病理结果为金标准比较两种方法在肺癌转移模型中的作用。结果经左心室注射luc+-PC-9细胞建立肺癌脑转移模型,脑转移成功率85%。肿瘤细胞的个数与发光强度呈正相关,具有较好的线性关系(R2=0.96)。生物发光成像能在颅脑、脊柱和股骨观察到荧光信号,病理结果证实为转移灶。^(18)F-FDG SPECT/CT在脑组织未见明显的代谢浓聚灶,在股骨或脊柱发现代谢浓聚灶,且病理证实均有骨髓转移。结论左心室注射法是建立人肺腺癌脑转移模型的可靠方法。生物发光成像系统在检测脑转移和骨转移具有较高的灵敏度和特异度,能实现实时、动态、无创观察转移瘤的生长情况;^(18)F-FDG SPECT/CT在检测脑转移灶并不具有优势,更适合于检测骨转移灶。Objective To establish a mouse model of lung adenocarcinoma brain metastasis with human luc＋-PC-9 cells stably expressing luciferase and to compare the evaluation values of bioluminescence imaging and18F-FDG（18F-fluorodeoxyglucose） SPECT / CT in these models. Methods Suspension of luc＋-PC-9 cells was injected into the left ventricle of BALB / c nude mice to establish a mouse model of brain metastasis from lung cancer. Bioluminescence imaging and18F-FDG SPECT / CT were used to evaluate the metastasis of tumors as compared with HE-staining pathology as a golden standard. Results The success rate of brain metastases was 85% through injecting luc＋-PC-9 cells into the left ventricle.The number of tumor cells was positively related to the intensity of light,with a linear correlation（ R2= 0. 96）. Fluorescence was observed in the brain,spine and femur by bioluminescence imaging,and the metastases were confirmed by HE pathological examination.18F-FDG SPECT / CT observed abnormal density collective foci in the spine or femur but not in the brain. Conclusions Injection of tumor cell suspension into the mouse left ventricle is a good method to establish a brain metastasis of lung cancer. Bioluminescence has a higher sensitivity and specificity in detecting brain metastasis and bone metastasis,with advantages of real-time,dynamical and non-invasive detection of tumor metastasis growth.18F-FDG SPECT / CT does not have superiority in detection of brain metastases but is suitable for detecting bone metastasis.

关 键 词：肺癌 脑转移 骨转移 动物模型 生物发光成像 单光子发射计算机断层成像术 

分 类 号：Q95-33[生物学—动物学]