Hepatic Arterial Chemoembolization With Arsenic Trioxide Eluting CalliSpheres Microspheres Versus Lipiodol Emulsion: Pharmacokinetics And Intratumoral Concentration In A Rabbit Liver Tumor Model

Abstract

Xu-hua Duan,* Hao Li,* Jian-zhuang Ren, Xin-wei Han, Peng-fei Chen, Feng-yao Li, Guo-hao Huang, Shu-guang Ju Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu-hua Duan; Jian-zhuang RenDepartment of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, 1 East Jianshe Road, Zhengzhou 450052, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]; [email protected]: The objective of this study was to investigate the plasma pharmacokinetic profiles, intratumoral concentration and tissue distribution of arsenic trioxide (ATO) by drug-eluting beads (DEB)-transcatheter arterial chemoembolization (TACE) compared with conventional TACE (cTACE) in a rabbit liver tumor model.Methods: Sixty-four rabbits with VX2 liver tumor were established and randomly assigned to four groups equally. The calliSpheres microspheres (CSM)-ATO group received DEB-TACE treatment using ATO-loaded CSM; the cTACE-ATO group received cTACE treatment using ATO mixed with lipiodol; the CSM-normal control (NC) group received DEB-TACE treatment using blank CSM; the TAE-lipiodol group received cTACE treatment using saline mixed with lipiodol. ATO concentration in plasma, tumor and normal tissues, and liver and kidney function indexes were evaluated.Results: The CSM-ATO group exhibited lower plasma ATO concentrations at 10 minutes and 20 minutes post treatment compared with the cTACE-ATO group. Meanwhile, intratumoral ATO concentrations were higher in the CSM-ATO group compared with the cTACE-ATO group at 3-, 7- and 14-days post treatment. In normal liver tissue, heart and muscle tissues, ATO concentrations between the CSM-ATO and cTACE groups were similar at each time point; in kidney and lung tissues, ATO concentrations were lower in the CSM-ATO group at 1-day post treatment while they were similar at 3, 7 and 14 days post treatment. Also, liver or kidney function indexes were of no difference at each time point between CSM-ATO and cTACE-ATO groups.Conclusion: Administration of ATO via DEB-TACE decreases systemic concentration while increasing intratumoral concentration of ATO without increasing liver or kidney toxicity compared with cTACE.Keywords: liver cancer, Arsenic trioxide, Transcatheter arterial chemoembolization, Drug-eluting beads, pharmacokinetics

Keywords

• liver cancer
• arsenic trioxide
• transcatheter arterial chemoembolization
• drug-eluting beads
• pharmacokinetics