Effect of Transcatheter Intraarterial Therapies on the Distribution of Doxorubicin in Liver Cancer in a Rabbit Model

BACKGROUND AND AIMS Transcatheter intraarterial techniques can effectively deliver chemotherapeutic agents to tumor and improve the efficacy of chemotherapy. The present study is designed to evaluate the effect of transcatheter intraarterial techniques on the distribution of doxorubicin in relation to blood vessels in liver cancer. METHODS VX2 tumors were implanted in the livers of 32 rabbits. The animals were divided into 4 groups of 8 animals each. Group 1 (doxo iv) animals received doxorubicin intravenous injection; group 2 (doxo ia) received doxorubicin hepatic intraarterial infusion; group 3 (doxo ia + E) received doxorubicin hepatic intraarterial infusion followed by embolization; group 4 (doxo + L ia + E) received hepatic intraarterial infusion of doxorubicin mixed with Lipiodol followed by embolization. Ten minutes or 4 hours after treatment, the animals were sacrificed and tumors were sampled. Immunofluorescence techniques were used to evaluate the distribution of doxorubicin in relation to blood vessels. RESULTS Doxorubicin fluorescence was distributed around tumor blood vessels and decreased with distance from the blood vessels. Tumor cells in avascular and adjacent regions were not exposed to detectable concentrations of doxorubicin. Tumors in the group 2, 3 and 4 had a significant increase in doxorubicin penetration compared with the group 1 tumors (P<0.05). Among the three groups of transcatheter therapies, doxorubicin penetration distance in group 3 was significantly larger than that in group 2 and 4 (P<0.05), and no significant difference was found between group 2 and 4 tumors (P>0.05) at 10 minutes. In contrast, at 4 hours and in total, both group 3 and 4 tumors had significant increases in drug penetration compared with group 2 (P<0.05), and no significant difference was noted between group 3 and 4 tumors (P>0.05). CONCLUSION Transcatheter intraarterial therapies improve doxorubicin penetration in liver cancer; nevertheless their effect on drug distribution is somewhat limited.