The antitumor effect and hepatotoxicity of a hexokinase II inhibitor 3-bromopyruvate: in vivo investigation of intraarterial administration in a rabbit VX2 hepatoma model

• Published in: Korean journal of radiology 2009, 10(6), , pp.596-603
• Main Authors: Jae, Hwan Jun, Chung, Jin Wook, Park, Hee Sun, Lee, Min Jong, Lee, Ki Chang, Kim, Hyo-Cheol, Yoon, Jung Hwan, Chung, Hesson, Park, Jae Hyung
• Format: Article
• Language: English
• Subjects: Animals; Catheters; Disease Models, Animal; Dose-Response Relationship, Drug; Doxorubicin - administration & dosage; Doxorubicin - pharmacology; Experiments; Glucose; Infusions, Intra-Arterial; Iodized Oil - administration & dosage; Iodized Oil - pharmacology; Liver cancer; Liver Neoplasms, Experimental - diagnostic imaging; Liver Neoplasms, Experimental - drug therapy; Medical imaging; Original; Pyruvates - administration & dosage; Pyruvates - pharmacology; Rabbits; Statistics, Nonparametric; Tomography, X-Ray Computed; Tumors; Veins & arteries; 방사선과학
• ISSN: 1229-6929; 2005-8330
• DOI: 10.3348/kjr.2009.10.6.596

The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. The tumor necrosis rate was significantly higher in the high dose group (93% +/- 7.6 [mean +/- SD]) than that in the control group (48% +/- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +/- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +/- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method.