Targeting of Different Ethiodized Oil–Doxorubicin Mixtures to Hypovascular Hepatic Metastases with Intraarterial and Intraportal Injections

Abstract

The distribution of different ethiodized oil-doxorubicin mixtures within and around hypovascular liver metastases in athymic nude mice was compared following either intraarterial or intraportal injections. Six different mixtures of doxorubicin and ethiodized oil in water-soluble contrast material, shaken for 5, 10, 15, and 30 minutes, respectively, were prepared and the size of the oil droplets in the mixtures evaluated. Intraarterial and intraportal injections of mixtures shaken for 10 and 15 minutes were performed in mice bearing hypovascular hepatic colorectal metastases. In vivo video microscopy was used to evaluate microvascular flow and the biodistribution and the size of the oil droplets within and around the tumors. Oil droplets smaller than 20 microns in diameter were taken up by tumor nodules. There was no significant difference in oil droplet accumulation within the tumor between intraarterial and intraportal injections. Oil droplets larger than 20 microns occluded small and medium portal branches. The optimum combination was 0.1 mL of ethiodized oil in 2 mL of diatrizoate sodium meglumine (Renografin-76) shaken for 15 minutes at 800 rpm, which formed droplets smaller than 20 microns (92%). Avascular regions of hepatic metastases may be embolized with ethiodized oil-anticancer drug mixtures containing oil droplets smaller than 20 microns. Since these droplets penetrate to the tumor interstitium with either intraarterial or intraportal injections, chemoembolization via the arterial route seems preferable for treatment of unresectable hypovascular hepatic metastases since it is easier to perform. The conclusions drawn from this study are limited to the animal model for experimental hypovascular hepatic metastases.