Objective To explore the therapeutic efficacy of 131I labeled anti-CD80 monoclonal antibody (4E5) in nude mice bearing human B-cell lymphoma.Methods The 4E5 was radiolabeled with 131I using the Iodogen method at room temperature,and the immune activity and stability of 131I-4E5 were analyzed.The lethal effects of 131I-4E5 and 4E5 against Raji cells were evaluated by MTT assay.Three tumorbearing nude mice were injected with 7.4 MBq of 131I-4E5 through tail vein,72 h later the mice were sacrificed and the ％ID/g was measured by calibrator and calculated.Fifteen tumor-bearing nude mice were randomly divided into 131I-4E5 group,4E5 group and normal saline control group according to different injections.The tumor inhibition rate was calculated 15 d post-injection,and then the mice were sacrificed to get tumor tissues for histopathological examination.One-way analysis of variance and two-sample t test were used to analyze the data.Results The labeling rate of 131I-4E5 was (78.3±2.4)％,the radiochemical purity was (95.7± 1.8)％ and specific activity was 579.4 GBq/g.The specific binding efficiency of 131I-4E5 with Raji cells was (36.1 ±2.6)％.131I-4E5 presented with a dose-dependent cytotoxicity against Raji cells.There were significant differences among the killing effects of different dosage groups (F=33.882,P＜0.001).Furthermore,131I-4E5 had higher growth inhibition rate on Raji cells than that of 4E5 (t:3.986-5.515,all P＜0.05).The biodistribution study showed that the tumor had high uptake of 131I-4E5,and the tumor/muscle ratio was 6.05± 1.20.The radioimmunotherapy results showed that the tumor growth suppression effect was more obvious in 131I-4E5 group and the tumor inhibition rate was 71.69％ on 15 d post-injection.The pathologic results showed necrosis in both 131I-4E5 group and 4E5 group,and the necrosis level was higher in 131I-4E5 group.Conclusion 131I-4E5 can target the tumor tissue and display an obvious antitumor effect in nude mice bearing human B-cell lymphoma.%目的 探讨131I标记的抗CD80单克隆抗体4E5(131I-4E5)对荷人淋巴瘤裸鼠的治疗效果.方法 采用Iodogen法进行4E5的131I标记,并对131I-4E5的免疫活性及稳定性进行分析;MTT法检测131I-4E5和4E5在体外对B淋巴瘤Raji细胞的杀伤效应.经荷瘤裸鼠尾静脉注入7.4 MBq(0.2 ml)的131I-4E5,72 h后处死荷瘤裸鼠,进行体内生物分布研究,计算各脏器或组织的放射性摄取(％ID/g).将荷瘤裸鼠按随机数字表法分为3组,分别经尾静脉注射131I-4E5、4E5及生理盐水对照,观察各组肿瘤生长情况,计算给药后15 d的肿瘤生长抑制率,然后处死荷瘤裸鼠,取肿瘤组织行常规病理分析.实验数据采用单因素方差分析及两样本t检验分析.结果 131I-4E5的标记率为(78.3±2.4)％,放化纯为(95.7±1.8)％,比活度为579.4 GBq/g;131I-4E5与Raji细胞的结合率为(36.1±2.6)％;131I-4E5对Raji细胞的杀伤作用呈剂量依赖性,差异有统计学意义(F=33.882,P＜0.001),不同剂量的131I-4E5对Raji细胞的抑制率均高于4E5(t:3.986～5.515,均P＜0.05).生物分布结果显示,肿瘤组织对131I-4E5有较高的摄取能力,肿瘤/肌肉比值为6.05±1.20;与对照组比较,131I-4E5组和4E5组的肿瘤生长均减慢,其中131I-4E5的肿瘤抑制效果更为明显,给药后15d时的肿瘤抑制率为71.69％.病理结果显示2组均可见肿瘤细胞坏死,其中131I-4E5组肿瘤细胞坏死更为明显.结论 131I-4E5在荷淋巴瘤裸鼠体内具有靶向定位能力,对肿瘤生长有明显的抑制作用,具有良好的RIT效果和潜在的临床应用价值.
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