结直肠癌人源性肿瘤组织异种移植模型(PDX)的构建及^(18)F-FDG PET/CT活体成像监测  

Establishment of colorectal cancer patient-derived xenograft (PDX) models and its characterization with ^(18)F-FDGPET/CT live imaging

作　　者：李武国[1] 陈伟[2] 任晖[2] 毕颎[3] 李文英 李观熳 赵广银[1] 李雯雯[1] 黄浩机 曹伟杰 戴伟刚 杨东杰[2] 何裕隆[1,2,4] 苏乔[1] LI Wu-guo;CHEN Wei;REN Hui;BI Jiong;LI Wen-ying;LI Guan-man;ZHAO Guang-yin;LI Wen-wen;HUANG Hao-ji;CAO Wei-jie;DAI Wei-gang;YANG Dong-jie;HE Yu-long;SU Qiao(Animal Experiment Center, the First Affiliated Hospital of Sun Yat-sen University, Guangdong Province Guangzhou 510080, China;Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangdong Province Guangzhou 510080, China;Laboratory of Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangdong Province Guangzhou 510080,China;the Seventh Affiliated Hospital of Sun Yat-sen University, Guangdong Province Shenzhen 518107)

机构地区：[1]中山大学附属第一医院动物实验中心,广东广州510080 [2]中山大学附属第一医院胃肠外科,广东广州510080 [3]中山大学附属第一医院外科实验室,广东广州510080 [4]中山大学附属第七医院,广东深圳518107

出　　处：《消化肿瘤杂志（电子版）》2017年第4期264-269,共6页Journal of Digestive Oncology(Electronic Version)

基　　金：广东省科技计划项目(2014A030304016;2017A030303015);国家自然科学基金面上项目(81672333)

摘　　要：目的构建结直肠癌人源性肿瘤组织异种移植模型(Patient-derived Xenograft,PDX),并探讨18F-FDG PET/CT成像技术用于监测结直肠癌PDX模型肿瘤生长的有效性。方法取外科手术切除的新鲜结直肠癌组织,接种到免疫缺陷小鼠皮下构建PDX模型。采用HE染色法、免疫组织化学染色法进行模型评价。选取部分构建成功的PDX模型进行PET/CT活体成像监测。结果接种结直肠癌患者新鲜肿瘤组织35例,成功构建PDX模型20例,成功率为57%;成瘤所需的中位时间为54.5天,四分位间距为47.5天。HE染色结果表明结直肠癌PDX模型可以较好地保留原发肿瘤的组织学特性。Ki67、p53在第一代PDX模型移植瘤与原发肿瘤组织中均呈强阳性表达,具有高度相似性。结直肠癌的成瘤能力与患者的性别、年龄、以及肿瘤的部位、大小、分期、分化程度等均没有相关性。PDX模型的PET/CT活体显像表明,18F-FDG PET/CT可以获得较好的显像效果。结论结直肠癌PDX模型构建成功率较高,模型可以较好地保留原发肿瘤的组织学、生物学特性。18F-FDG PET/CT成像技术可用于监测结直肠癌PDX模型肿瘤的生长情况。韵遭躁藻糟贼蚤增藻To establish and characterize the patient-derived xenograft渊PDX冤models for colorectal cancer,and investigate the effectiveness of18F-FDG PET/CT imaging technique in the monitoring PDX tumor growth.Methods Fresh surgically removed tumor tissues from colorectal cancer patients were sam鄄pled and inoculated into immunodeficient mice subcutaneously to establish PDX models.HE and immunohisto鄄chemical staining were used to evaluate the established PDX tumors.Two PDX models were selected for PET/CT live imaging analysis.Results Tumor tissues from35cases of colorectal cancer patients were inoculated into mice,20of which generated PDX tumor,with a success rate of57%.The median time to successful PDX estab鄄lishment was54.5days,with interquartile range47.5days.The results of HE staining showed that the PDX models of colorectal cancer could preserve the histological characteristics of primary tumor.Ki67and p53were strongly positive in both first generation PDX model and primary tumor tissues,and they had high similarity.The rate of successful PDX model establishment was not associated with patient gender,age,nor with the location,size,stage and differentiation of primary tumors.PET/CT was used to visualize two PDX models.18F-FDG PET/CT imaging showed good results in assessing the size and metabolism of established PDX tumors.Conclusion Colorectal cancer PDX models is easy to establish,and can retain the histology and biological characteristics of primary tumors.18F-FDG PET/CT can be used for monitoring tumor growth of colorectal cancer PDX models.

关 键 词：结直肠癌 人源性肿瘤组织异种移植模型 PET/CT 18F-FDG 

分 类 号：R735.34[医药卫生—肿瘤]