Novel Intraarterial Therapy for Liver Cancer Using Ethylbromopyruvate Dissolved in an Iodized Oil
- Novel Intraarterial Therapy for Liver Cancer Using Ethylbromopyruvate Dissolved in an Iodized Oil
- 최영호; 정진욱; 손규리; 소영호; 김원; 윤창진; 윤정환; 정혜선; 김효철; 제환준; 김영일; 박재형
- 간암; 간동맥색전술; 에틸브로모피루베이트; Ethylbromopyruvate; hexokinase II inhibitor; intraarterial chemotherapy; VX2 carcinoma; liver cancer
- Issue Date
- Academic radiology
- VOL 18, NO 4, 471-478
- Rationale and Objectives: In spite of various therapies developed, hepatocellular carcinoma still shows poor prognosis. In this study, we introduced ethylbromopyruvate (EBrP), a hydrophobic derivative of 3-bromopyruvate, as an agent for intraarterial therapy of hepatocellular
Materials and Methods: In in vitro study, we evaluated whether EBrP induced apoptotic cell death in Huh-BAT cells. Chemical degradation products of EBrP were identified by performing proton nuclear magnetic resonance spectroscopy and thin layer chromatography. VX2 carcinoma was implanted and grown in the liver of 25 rabbits for in vivo study. By transfemoral intraarterial approach, 0.4 mL of 10 mM and 40 mM EBrP dissolved in an iodized oil (Lipiodol) was infused into the proper hepatic artery in 8 and 10 rabbits, respectively. In the remaining seven rabbits, 0.4 mL of Lipiodol alone was intraarterially injected as a control. One week later, tumor necrosis rate was calculated with histopathologic examination and hepatotoxicity was evaluated with biochemical analysis.
Results: EBrP induced apoptosis in human HCC cells via mitochondrial apoptotic signaling cascades. EBrP dissociated into 3-bromopyruvate and ethanol in the aqueous environment. In VX2 liver tumor models, the group of intraarterial delivery of 40mMEBrP/Lipiodol solution showed higher tumor necrosis rates (96.1% ± 3.8) than the other groups (38.9% ± 15.9 of a control, 90.5% ± 2.9 in 10 mM) (P < .05). There was transient elevation of AST and ALT enzyme levels without any mortality.
Conclusions: Intraarterial infusion of EBrP/Lipiodol solution is a feasible intraarterial therapy for liver tumors with potent antitumor effects and transient hepatotoxicity.
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