靶向制剂＾131I-Anti-EGFRvⅢ的制备及其在恶性胶质瘤裸鼠中的显像分布  

Preparation of ^131I-Anti-EGFRv III and its imaging distribution in malignant glioma-loading nude mice

作　　者：安雷[1] 魏大年[1] 黄凯[2] 张冠华[1] 朱永晖[1] 刘铁坚[1] 刘承勇[1] 

机构地区：[1]南方医科大学第三附属医院神经外科,广州510630 [2]南方医科大学南方医院核医学科,广州510515

出　　处：《中华神经医学杂志》2016年第9期878-883,共6页Chinese Journal of Neuromedicine

基　　金：广东省自然科学基金（S2011010005324）

摘　　要：目的探讨放射性核素碘131（^131I）标记表皮生长因子受体Ⅲ型突变体抗体（Anti-EGFRvⅢ）的实验方法、条件以及标记产物^131I-Anti-EGFRvⅢ在恶性胶质瘤裸鼠体内的靶向性分布。方法采用Iodogen法进行Anti-EGFRvⅢ的^131I标记，SephadexG-50层析柱层析分离各组分．纸层析法测定标记产物的放射化学纯度及体内、外稳定性。选取肿瘤平均直径在10-15mm的U87-EGFRvⅢ胶质瘤模型裸鼠28只，按随机数字表法分为静脉注射^131I-Anti-EGFRvⅢ组，静脉注射^131I组，瘤内注射^131I-Anti-EGFRvⅢ组，瘤内注射^131I组，每组7只，分别经尾静脉和瘤内注射7．5MBq／0.1mL标记产物^131I-Anti-EGFRvⅢ和^131I,应用单光子发射计算机断层成像术（SPECT）扫描观察标记产物在胶质瘤裸鼠体内的放射性分布特点。结果^131I标记Anti—EGFRvⅢ的标记率为（68．12±6．19）％：纯化后纸层析法测得^131I-Anti—EGFRvⅢ的即刻放射化学纯度为（95．12±0．591％，分别在室温和37℃血清中放置1、2、4、12、24h后放射化学纯度比较差异均无统计学意义（P〉0．05），其中放置24h后放射化学纯度分别为（87．78±5.351％和（85．12±3．581％。SPECT显像扫描显示无论是通过尾静脉注射还是瘤内注射标记产物^131I-Anti-EGFRvⅢ，肿瘤部位均可见较强烈的放射性显像，而甲状腺基本不显像。结论Iodogen法适用于Anti-EGFRvⅢ的^131I标记。标记的产物^131I-Anti-EGFRvⅢ具有良好的放射化学纯度和稳定性，能够与肿瘤组织特异性结合,具有良好的靶向性。Objective To explore the experimental methods and conditions of ^131I-labeled anti-epidermal growth factor receptor （EGFR） vⅢ preparation, and to evaluate the targeting distribution of ^131I-Anti-EGFRvⅢ in malignant glioma-loading nude mice. Methods The ^131I labeling on anti-EGFRvⅢ was performed by Iodogen method. The labeling rate was determined after separation and purification and paper chromatography was used for the determination of radioactive chemical purity. Twenty-eight U87-EGFRvⅢ malignant glioma-loading nude mice with glioma average diameter of 10-15 mm were chosen and randomly divided into group of ^131IAnti-EGFRvⅢ intravenous injection, group of Na^131I intravenous injection, group of ^131I-Anti-EGFRvⅢ intratumor injection and group of Na^131I intratumor injection; 7.5 MBq/0.1 mL labeled products with ^131I-Anti-EGFRvⅢ or Na^131I were injected in the veins or the tumors to observe the changes of the radioactivity distribution of malignant glioma-loading nude mice with SPECT imaging. Results The rate of ^131I-labeled anti-EGFRvIII was （68.12±6.19）%, and the immediate rate of radiochemical purity was （95.12±0.59）%, and （87.78 ±5.35）% in room temperature and （85.12±3.58）% in 37℃ serum placed for 24 h. SPECT scan showed that the tumor site had significantly stronger imaging than the thyroid gland with the labeled products either by intravenous or intratumor injection. Conclusions It is applicable to the ^131I-labeled Anti-EGFRvⅢ with Iodogen method. ^131I-Anti-EGFRvⅢ has good radiation chemical purity and stability in vitro and in vivo, and could be combined with tumor tissue specificity.

关 键 词：神经胶质瘤 碘131 表皮生长因子受体Ⅲ型突变体抗体 放射性核素显像 

分 类 号：R739.41[医药卫生—肿瘤]