Radioimmunotherapy of 131I-4E5 in nude mice bearing human B-cell lymphoma

Abstract

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 tumor-bearing 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. Key words: Lymphoma, B-cell; Radioimmunotherapy; Antibodies, monoclonal; Isotope labeling; Iodine radioisotopes; Mice, nude