^131I-Herceptin在荷人乳腺癌裸鼠模型中的生物分布及抗肿瘤活性研究  

Experimental study on biodistribution and anticancer activity of ^131I-Herceptin in breast cancer xenograft

作　　者：范义湘[1] 石卫民[1] 罗荣城[2] 高梅菊[1] 刘青竹[1] 李科斌[1] 吴继珍[1] 

机构地区：[1]广东省第二人民医院核医学科,广州510317 [2]南方医科大学南方医院肿瘤中心

出　　处：《中华核医学杂志》2009年第5期311-315,共5页Chinese Journal of Nuclear Medicine

基　　金：广东省自然科学基金（037050）

摘　　要：目的探讨^131I-Herceptin在荷人乳腺癌裸鼠模型中的生物分布及其对人表皮生长因子2（HER2）高表达乳腺癌的放射免疫治疗疗效。方法^131I-Herceptin采用Iodogen法制备。15只HER2高表达乳腺癌裸鼠模型分为3组：^131I-Herceptin组、Herceptin组与空白对照组，每组5只。以肌肉为参照，注射后第3，6，9天显像观察肿瘤等组织的放射性摄取并计算肿瘤／肌肉（T／M）比值。注射后1～9d，测量肿瘤大小并计算肿瘤抑制率。第9天处死裸鼠，剥离肿瘤，计算肿瘤的每克组织百分注射剂量率（％ID／g）值并以Western—Blot法、反转录-聚合酶链反应（RT—PCR）法检测肿瘤组织HER2及癌胚抗原（CEA）蛋白及基因表达水平的变化。肿瘤T／M比值与其他脏器的差别、HER2及CEA基因表达水平、蛋白表达水平在各治疗组间的差异采用One—way ANOVA检验；^131I-Herceptin组和Herceptin组肿瘤抑制率的差异采用t检验。结果^131I-Herceptin的放化纯为94％，比活度约为37kBq／μg，在注射后第9天，T／M比值达4．11，显著高于其他组织（F=12．370，P〈0．05）；肿瘤摄取分数为（16．1±1．7）％ID／g，高于其他组织、器官（F=166．150，P〈0．01）。至治疗后9d，^131I-Herceptin组抑瘤率显著高于Herceptin组[（42．0±6．9）％与（23．2±3．8）％，t=5．321，P〈0．001]。^131I-Herceptin组HER2蛋白表达（0．435±0．087与0．557±0．043，t=2．811，P〈0．05）与基因表达（0．256±0．073与0．350±0．029，t=2．678，P〈0．05）均显著低于Herceptin组。^131I-Herceptin组CEA蛋白表达（0．537±0．048与0．607±0．029，t=2．800，P〈0．05）与基因表达（0．362±0．048与0．607±0．079，t=5．932，P〈0．001）均显著低于Herceptin组。结论^131I-Herceptin对HER2高表达的乳腺癌具有很高的靶向特性，能比Herceptin更有效地抑制乳腺癌细胞分裂、增殖、分化、存活，控制肿瘤生长。Objective Herceptin is a kind of anti-human epidermal growth factor receptor 2 （HER2） humanized monoclonal antibody and was largely applied in metastatic breast cancer with HER2 overexpressing. The clinical effective though better than concurrent chemoradiotherapy, but was still not satisfied due to cell transformed. ^131I-Herceptin may be of some help in elevation the control rate due to the cytotoxic effect from ^131 I. The aim of this study was to evaluate the radioimmunotherapy for HER2 overexpressing metastatic breast cancer using ^131I-Herceptin. Methods Herceptin was labelled to ^131 I with the Iodogen method. The mice bearing with breast cancer were divided into three groups. One was ^131I-Herceptin, another was Herceptin, and the other was control. The biodistribution of ^131I-Herceptin in breast cancer xenograft was measured by radioimmunoimaging on the 3rd, 6th and 9th day after injection. The radioactivity of tumor to muscle （T/M） ratio was calculated and compared. From 1-d to 9-d, the inhibitory rate of tumor growth was calculated and compared. On the 9-d, the tumors of each group were desquamated and the percentage activity of injection dose per gram of tissue （ % ID/g） was calculated and compared. Protein and gene expression of HER2 and carcinoembryonic antigen （CEA） were compared. One-way ANOVA was applied for statistical analyses. Results The radiochemical purity of ^131 I-Herceptin was 94%. The imaging manifestation indicated that the uptake of ^131I-Herceptin in tumor was higher than that in other organs, the T/M ratio achieved to the highest level of 4.11 on 9-d （F = 12. 370, P 〈0.05）. On 9-d, tumor showed that highest % ID/g （F = 166. 150, P 〈0.01 ） as （16.1± 1.7）%. The inhibitory rate showed significant difference on 9-d [ （42.0± 6.9）% vs （23.2 ± 3.8 ）% , t = 5. 321, P 〈 0.001 ] between groups A and B. The protein expression （0. 435 ± 0. 087 vs 0. 557 - 0. 043, t = 2. 811, P 〈 0.05 ） and gene expression （ 0. 256 ± 0. 073 vs 0. 350 ± 0.

关 键 词：乳腺肿瘤 放射免疫疗法 抗体 单克隆 表皮生长因子-尿抑胃素 同位素标记 碘放射性同位素 小鼠 裸 

分 类 号：R686[医药卫生—骨科学]