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

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 HEB2 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 131I. The aim of this study was to evaluate the radioimmunotherapy for HER2 overexpressing metastatic breast cancer using 131I-Herceptin. Methods: Herceptin was labelled to mi with the Iodogen method. The mice bearing with breast cancer were divided into three groups. One was 131I-Herceptin, another was Hereeptin, 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 131I-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 ± 0.029, t=2.678, P<0.05) of HER2 in 131I-Herceptin were significantly lower than that in Herceptin groups. Similarly, the protein expression (0.537 ± 0.048 vs 0.607 ± 0.029, t= 2.800, P<0.05) and gene espression (0.362 ± 0.048 vs 0.607 ± 0.079, t=5.932, P<0.001) of CEA in 131I-Herceptin group were significantly lower than that of Herceptin group. Conclusions: 131I-Herceptin accumulates mainly in tumor and takes on remarkable targeting property to seek tumor with HER2 overexpression. It may inhibit the proliferation of breast cancer cells more effectively than Herceptin. (authors)