Using anti-VEGF monoclonal antibody and magnetic nanoparticles as double-targeting vector for the radioimmunotherapy of liver cancer

Objective To study the biodistribution of 131I-anti-vascular endothelial growth factor (VEGF) monoclonal antibody (Sc-7269)-dextran magnetic nanoparticles (DMN) in nude mice bearing human liver cancer where an external magnetic field was focused on, and to evaluate its therapeutic effects and safety. Methods Eighteen nude mice bearing human liver cancer where an external magnetic field was focused on, were used for the biodistribution study after intratumoral injection (n=9) or intravenous injection (n=9) of 131I-Sc-7269-DMN. Another 25 tumor-bearing nude mice were divided into five groups, four groups of them were treated with 74 MBq/ml 131I-Sc-7269-DMN, 131I-Sc-7269, 131I-DMN and 131I by a single intratumoral injection, respectively. And an external magnetic field was bound to the tumor of the nude mice that were injected 131I-Sc-7269-DMN or 131I-DMN. For control study, the remaining one group was injected with physiological saline. Tumor growth delay (TGD) and tumor inhibition rate were observed as antitumor effects. Peripheral white cell counts and the loss of body weight were tested as indicators of systemic toxicity. Results The retention percentages of radioactivity (%ID/g) in tumors after intratumoral injection were 104.06, 101.58 and 100.96 %ID/g at 4, 24 and 48 h, respectively, while in the case of intravenous injection, the %ID/g values were lower (85.33, 89.67 and 90.00 %ID/g, respectively, P0.05), and all were much higher than that in normal organs evaluated. TGD in the nude mice treated with 131I-Sc-7269-DMN [(13.3±3.3) d] was the longest, and tumor inhibition rate (89.0%)was the highest compared with that in other groups (P0.05). However, systemic toxicity was not significantly increased in 131I-Sc-7269-DMN-treated mice as monitored by the decrease in peripheral white cell counts and the loss of body weight. Conclusions The radioimmunotherapy with intratumoral injection of 131I-Sc-7269-DMN may be safe and efficient for the treatment of liver cancer. Furthermore, the radioimmunotherapy using DMN as a carrier system may be a highly potential approach in targeted treatment of other kinds of tumors.