Combination of 131I-anti-endoglin monoclonal antibody and 5-fluorouracil may be a promising combined-modality radioimmunotherapy strategy for the treatment of hepatocellular carcinoma

Abstract

The present study aimed to investigate the therapeutic efficacy of combined radioimmunoconjugate 131I endoglin (ENG) and 5-fluorouracil (5-FU) in mouse model with hepatocellular carcinoma (HCC). HCC tumour SMMC7721-GFP xenograft-bearing mice were established and divided into four groups: control group, 5-FU group, 131I-anti-ENG McAb group, and 5-FU and 131I-anti-ENG McAb combination group. 5-FU or 131I-anti-ENG McAb was intraperitoneally injected from Monday to Friday with a therapy break on Saturday and Sunday. So was the combination therapy with 5-FU and 131I-anti-ENG McAb. 131I-anti-ENG McAb and131I-IgG were prepared, and their biodistribution was studied. Noninvasive fluorescence imaging, tumour volume and tumour weight were measured. High expression levels of ENG in HCC tissues were confirmed by whole-body phosphor-autoradiography. Whole-body phosphor-autoradiography also showed higher tumour uptake for 131I-anti-ENG McAb compared with 131I-IgG. Biodistribution studies indicated higher tumour accumulation and better T/NT (6.44 ± 1.01) of 131I-anti-ENG McAb. Noninvasive fluorescence imaging revealed significant tumour growth suppression in the 131I-anti-ENG McAb and 5-FU combination therapy group based on reduced fluorescent signals. After treatment with 131I-anti-ENG McAb and 5-FU, the tumour volume and tumour weight were all decreased. The tumour growth inhibition rate was up to 77.1 ± 4.06% in the 131I-anti-ENG McAb and 5-FU combination therapy group. The present study demonstrated that the combination of 131I-anti-ENG McAb and 5-FU may be a promising combined-modality radioimmunotherapy strategy for HCC.

Keywords

• 131I
• combination therapy
• radioimmunotherapy
• antiangiogenic therapy
• endgolin
• 5-fluorouracil
• hepatocellular carcinoma