Heesun Park MD, Presenter: Nothing to Disclose

Jin Wook Chung, Abstract Co-Author: Nothing to Disclose

Hwan Jun Jae MD, Abstract Co-Author: Nothing to Disclose

Young Il Kim MD, Abstract Co-Author: Nothing to Disclose

Ki Chang Lee DVM, Abstract Co-Author: Nothing to Disclose

Jae Hyung Park, Abstract Co-Author: Nothing to Disclose

Hexokinase II, the first-step enzyme of the glycolytic pathway, is overexpressed in highly malignant cells. Recently, there was a report that intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BP) is safe and effective in treating hepatic VX2 carcinoma of rabbits. The purpose of this study was to compare antitumor effect of intraarterial delivery of low- and high-dose 3-BP and those of conventional Lipiodol-doxorubicin emulsion in rabbit VX2 hepatoma model.

VX2 carcinoma was implanted in livers of 21 rabbits. Transcatheter intra-arterial administration was performed using low dose 3-BP (25mL in 1mM concentration, n=6), high dose 3-BP (25mL in 5mM concentration, n=6), Lipiodol-doxorubicin emulsion (1.6mg doxorubicin/0.4mL Lipiodol, n=6), and as a control group, 3 rabbits were treated with normal saline alone. One week later, proportion of tumor necrosis was calculated based on histopathologic examination. Hepatotoxicities were evaluated by biochemical analysis. Differences between these groups were statistically assessed with Mann-Whitney U tests.

Tumor necrosis rate was significantly higher in high dose group (90.5%±8.7 [mean±SD]) than in the control group (63.1%±14.9)(P=.024), but not significantly higher in low dose group (69.5%±16.6)(P=.381). However, tumor necrosis rate of high dose group was significantly lower than that of Lipiodol-doxorubicin treatment group (98.6%±3.47)(P=.015). Hepatotoxicity was dose-dependent but transient in all rabbits.

Even though intra-arterial delivery of 3-BP showed dose-dependent anti-tumor effect, single session treatment seems to have limited efficacy when compared with the conventional method. Further studies for optimal treatment protocol to enhance therapeutic effect are warranted.

Park, H, Chung, J, Jae, H, Kim, Y, Lee, K, Park, J, The Anti-tumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor, 3-Bromopyruvate: Part II—In Vivo Investigation in Rabbit VX2 Hepatoma Model through Intraarterial Administration.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4416014.html