^(131)I标记抗肺癌单克隆抗体1E2在荷瘤小鼠体内分布及对小鼠移植瘤作用

The Biodistribution of Anti-lung Cancer Monoclonal Antibody 1E2 Labeled with ^(131) I in Tumor Bearing Mice and Its Therapeutic Effects on Transplanted Tumors in Mice

目的:分析碘-131(131I)标记抗肺癌单克隆抗体1E2在荷Lewis肺癌小鼠体内分布,评估瘤内注射碘-131标记抗肺癌单克隆抗体1E2(131I-1E2)对小鼠Lewis肺癌的生长抑制作用。方法:C57BL/6小鼠右后腿皮下接种Lewis肺癌细胞(LLC)1×106/只,建立荷Lewis肺癌小鼠模型,免疫组化检测Lewis肺癌细胞(LLC)膜上1E2抗原-氨甲酰磷酸合成酶1(CPS1)的表达。131I标记1E2单抗(氯胺T法),检测标记率、放化纯度、放射性比活度。荷瘤小鼠尾静脉注射标记抗体131I-1E218.5MBq,观察其不同时间点在小鼠体内的分布。成瘤后小鼠随机分为4组,分别瘤内注射生理盐水0.1ml(空白对照),1E2单抗3μg(阳性对照),131I-IGg18.5MBq(阴性对照),131I-1E218.5MBq。治疗后每周2次测定肿瘤大小,21天后处死小鼠观察肿瘤组织病理学改变,检测肿瘤体积、重量,计算抑瘤率。结果:1E2抗原-CPS1主要在肿瘤细胞膜表达,131I-1E2标记率为67.73%,放化纯度为95.63%。131I-1E2主要分布在肿瘤组织,治疗后3周试验组肿瘤体积为(0.75±0.15)cm3,重量为(1.60±0.19)g,抑瘤率78.30%,与对照组间比较差异有统计学意义(P<0.01),对照组之间差异无统计学意义(P>0.05)。治疗组与对照组间病理学差异显著。结论:131I-1E2瘤内注射可抑制肿瘤的生长,具有潜在的临床应用价值,有可能成为新的肿瘤治疗靶向药物。

Objective： To observe the biodistribution of anti-lung cancer monoclonal antibody 1E2 labeled with ^131 Ⅰ in mice bearing Lewis lung cancer and to evaluate the inhibitory effect of this antibody on Lewis lung carcinoma. Methods： The animal model was established by subcutaneous inoculation of Lewis lung cancer cells （1×10^6） to the right hind legs of C57BL/6 mice. The expression of the 1E2 antigen, also known as carbamoyl phosphate synthetase 1 （CPS1） on the Lewis lung carcinoma cell membrane, was detected by immunohistochemistry. The 1E2 monoclonal antibody was radioiodinated with ^131 Ⅰ using the chloramine T method. The labeling ratio, radiochemical purity and specific radioactivity of the labeled antibody were detected. After tail intravenous injection of 18.5 MBq 1311-1E2, the biodistribution of ^131 Ⅰ-lE2-1abeled antibody in mice at different time points was observed. After tumor model establishment, all of the mice were randomly divided into 4 groups （n= 10）. When the tumor reached 0.5-0.7 cm in diameter, intratumoral injection of 0.1ml physiological saline （Blank control）, 3μg 1E2 （Positive control）, 18.5 MBq ^131 Ⅰ-IgG （Negative control）, or 18.5 MBq ^131 Ⅰ-1E2 （Experimental group） were administered on day 0, 7 and 14. The tumor size and volume were measured twice a week before and after treatment. The tumor inhibitory rate was calculated. After 21 days, the mice were sacrificed for pathological examination of the tumor. Results： The 1E2 antigen （CPS1） was mostly expressed on tumor cell plasmalemma. The labeling ratio of the ^131 Ⅰ-1E2 antibody was 67.73%, the radiochemical purity was 95.63%, and the radioactivity concentration of ^131 Ⅰ-1E2 was mainly distributed to the tumor tissues. The gross tumor volume of the experimental group was 0.746±0.153 cm^3, the tumor weight was 1.602±0.194 g, and the inhibitory rate was 78.3% at 3 weeks after treatment. A significant difference was found in the gross tumor volume, tumor weight, and inhibitory rate at 3 weeks after treatment between the experimental group and the control groups. Conclusion： ^131 Ⅰ-1E2 antibody has the ability to target tumor cells and therefore can effectively inhibit tumor growth in vivo. ^131 Ⅰ-1E2 possesses potential clinical application value and may become a new drug for targeted cancer therapy.