The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model.
10.3348/kjr.2009.10.6.596
- Author:
Hwan Jun JAE
1
;
Jin Wook CHUNG
;
Hee Sun PARK
;
Min Jong LEE
;
Ki Chang LEE
;
Hyo Cheol KIM
;
Jung Hwan YOON
;
Hesson CHUNG
;
Jae Hyung PARK
Author Information
1. Department of Radiology, Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center and Clinical Research Institute, Seoul National University Hospital, Korea. chungjw@radcom.snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Hepatocellular carcinoma;
3-Bromopyruvate;
Hexokinase II inhibitor;
Intraarterial chemotherapy;
VX2 carcinoma
- MeSH:
Animals;
Disease Models, Animal;
Dose-Response Relationship, Drug;
Doxorubicin/administration & dosage/pharmacology;
Infusions, Intra-Arterial;
Iodized Oil/administration & dosage/pharmacology;
Liver Neoplasms, Experimental/*drug therapy/radiography;
Pyruvates/administration & dosage/*pharmacology;
Rabbits;
Statistics, Nonparametric;
Tomography, X-Ray Computed
- From:Korean Journal of Radiology
2009;10(6):596-603
- CountryRepublic of Korea
- Language:English
-
Abstract:
OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
