Transcatheter hepatic arterial infusion with 131I-anti-CD147-monoclonal-antibody on treating liver cancer in a rabbit model

Abstract

Objective To evaluate the efficacy and safety of treating liver cancer using 131I-anti-CD147-monoclonal-antibody (131I-anti-CD147-McAb) by transcatheter hepatic arterial infusion (TAI) in a rabbit liver cancer model. Methods Forty-five rabbit models were randomly divided into three groups evenly. Transcatheter hepatic artery infusion under general anesthesia were performed in all three groups. Group A: control group, saline. Group B: pure 131I solution. Group C: 131I-anti-CD147-McAb solution. About 2 ml blood sample was obtained from all rabbits for liver, kidney, and thyroid function at pre-TAI and post-TAI 1 day, 3 days, 7 days, 14 days, 21 days. The rabbits were scanned by single photon emission computed tomographic (SPECT) to monitor radionuclide bio-distribution and tumor size on 1 day, 7 days, 14 days, 21days after procedures in group B and C. On 14 days after procedure, five rabbits were randomly selected to be sacrificed in each group for pathological and immunological investigations. The remaining rabbits continued to be fed, and survival rates were measured. Results The TAI and SPECT-CT/CT procedures were successfully performed in all rabbits. Test results showed that AST and ALT levels tended to increase transiently 1 day after TAI (P 0.05) 7 days after TAI. FT3 and FT4 mean values of rabbits in group B and C continued to decline 7 days after TAI, while thyroid stimulating hormone (TSH) showed corresponding increase (P 0.05). SPEC-CT imaging of rabbits shows that most of the radionuclide was gathered in the gastrointestinal tract and thyroid in Group B, however, radionuclide was mainly concentrated in the tumor lesions in Group C. Fourteen days after procedures, radionuclide imaging of all rabbits disappeared in group B and C. The VX2 liver tumors increased rapidly after treatment in group A and B; but the tumors gradually reduced their size in group C. At 14 days after TAI: The proportion of tumor necrosis in group C was significantly greater than that in groups A and B (P<0.05). The microvessel density (MVD) number of residual tumor in group C was less than groups A or B (P<0.05).TUNEL analysis suggested that more apoptosis bodies was displayed in the residual tumor tissue in group C than that in groups A and B, but the expression of MMP-2 and vessel endothelial grouth factor (VEGF) was significantly reduced in group C than group A and group B. Median survival time of the rabbits in groups A, B, C was 22 days, 26 days and 54 days respectively. Survival time of the rabbits in group C was significantly prolonged than other two groups (P<0.01). Conclusions Radioimmunotherapy with 131I-anti-CD147-McAb by TAI can inhibit the growth and metastasis of liver cancer, and prolong the survival of experimental animals. The method is effective and safe in this animal study. Key words: Liver neoplasms, experimental; Antineoplastic protocols; Radiology, interventional; Radioimmunotherapy