Hepatic arterial chemoembolization with arsenic trioxide eluting callispheres microspheres versus lipiodol emulsion: Pharmacokinetics and intratumoral concentration in a rabbit liver tumor model

Abstract

Background: The objective of this study was to investigate the plasma pharmacokinetic profiles, intratumoral concentration and tissue distribution of arsenic trioxide (ATO) by drugeluting 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 DEBTACE 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 andmuscle 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.