Improved drug targeting to liver tumors after intra-arterial delivery using superparamagnetic iron oxide and iodized oil: Preclinical study in a rabbit model

摘要

Purpose: The purpose of this study was to evaluate the feasibility and the therapeutic efficacy of a novel drug-delivery system that uses superparamagnetic iron oxide (SPIO) and iodized oil (IO) to improve the selective intra-arterial (IA) drug delivery to an experimentally induced hepatic tumor. Materials and Methods: This animal study was approved by our institutional animal care and use committee. Fifteen rabbits with hepatic VX2 carcinomas were treated with IA delivery of 4 different agents: doxorubicin alone (group A, n = 3), doxorubicin/IO (group B, n = 3), a doxorubicin/SPIO complex (group C, n = 4), and a doxorubicin/SPIO/IO complex (group D, n = 5). The infused doxorubicin dose was 1 mg for all groups. The serum doxorubicin concentration was measured at 0, 5, 30, 60, and 120 minutes after the delivery. To assess the distribution of the SPIO, magnetic resonance (MR) scans were performed at day 7 after the delivery, when computed tomographic scans were performed in addition to MR in group B and D to assess the distribution of IO. After the completion of follow-up imaging, all the animals were euthanized to measure the intratumoral doxorubicin concentration and to assess tumor viability through pathologic examination. Results: Groups C and D demonstrated significantly lower MR signal intensities, which inversely corresponded to SPIO deposition, in the tumor areas than did groups A and B. Group D exhibited the lowest serum doxorubicin concentration at all time points up to 180 minutes after the delivery, suggesting minimal passage of doxorubicin into the systemic circulation. The intratumoral doxorubicin concentrations were 72.4 ng/g for group A, 142.0 ng/g for group B, 264.1 ng/g for group C, and 679.6 ng/g for group D. The proportion of viable tumor cells were 65.3% for group A, 1.3% for group B, 17.0% for group C, and 0.1% for group D. Conclusions: The drug-delivery system developed using SPIO and IO can result in better drug targeting when it is used for IA delivery to liver cancer. The results of this study warrant further investigation of this potential clinical treatment of advanced liver cancer.