Abstract No. 329 Caffeic Acid, a Novel Anti-metabolic Agent, in Transarterial Embolization of a Woodchuck Model of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) uses both aerobic and anaerobic metabolism. This study evaluates transarterial embolization (TAE) and transarterial chemoembolization (TACE) with lactate transport inhibitor caffeic acid (CA) in a woodchuck (Marmota momax) de novo tumor model. Woodchucks with HCC resulting from hepatitis infection were divided into three groups: Control group (n=9, 1 mL of normal saline, NS), bland TAE (n=10, 1 mL of ethiodized oil), and TACE (n=7, 0.5 mL Lipiodol + 0.5 mL CA in NaOH (total 10 mg CA)). Embolization to angiographic stasis was performed through a microcatheter at the segmental level. Tumor volume was measured by magnetic resonance imaging (MRI) before treatment and once a month for 6 months. Tumor perfusion was quantified by sequential contrast-enhanced MRI images obtained every 15s for a duration of 150 sec. Using semi-automated tumor ROI, intensity values were measured at representative axial slices at each time point. Area under the curve was then calculated to represent overall tumor perfusion. After 6 months, animals were euthanized and the tumors underwent histopathologic analysis. There was no significant difference in the initial tumor sizes. The control group and the ethiodized oil TAE group both showed rapid growth with volumes that were 2,130% larger and 712% larger respectively. The ethiodized oil + CA TACE group showed a 10.2% decrease in volume compared with baseline (p < 0.05). The TACE group also demonstrated a statistically significant reduction in tumor perfusion between the pre-operative and immediate post-operative timepoints when compared with the NS controls (125%, p < 0.05). Histopathologic analysis revealed marked reduction in viable tumor tissue comparing TACE to TAE and control groups. Antimetabolic TACE therapy using ethiodized oil + CA is an effective treatment for HCC in a woodchuck animal model. Our trial demonstrated significant tumor response through marked reductions in tumor volume and tumor viability. These data support advancing to a clinical trial.