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


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.


CONCLUSIONS
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.
Jae
Hwan Jun
HJ
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.
Chung
Jin Wook
JW
Park
Hee Sun
HS
Lee
Min Jong
MJ
Lee
Ki Chang
KC
Kim
Hyo-Cheol
HC
Yoon
Jung Hwan
JH
Chung
Hesson
H
Park
Jae Hyung
JH
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D007459:Iodized Oil / Q000008:administration & dosage / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011773:Pyruvates / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D018709:Statistics, Nonparametric; D014057:Tomography, X-Ray Computed
D011773:Pyruvates; C017092:bromopyruvate; D007459:Iodized Oil; D004317:Doxorubicin