Hepatic Arterial Chemoembolization With Arsenic Trioxide Eluting Calli Spheres Microspheres Versus Lipiodol Emulsion:Pharmacokinetics And Intratumoral Concentration In Rabbit Liver Tumor Models

PurposeTo study pharmacokinetics and tissue distribution of CalliSpheres Beads(CB)loaded Arsenic trioxide(ATO)on rabbit VX2 liver tumor by transcatheter arterial chemoembolization.Materials and Methods64 rabbits with VX2 liver tumors were randomly divided into 4 groups of 15 animals each: control group,CB group,CBATO group and cTACE group.Blood samples were taken at different time points after TACE and blood concentration,liver and kidney function were examined respectively.4 rabbits were sacrificed at 1,3,7 and 14 days after operation in each group.The tumor,liver,kidney,lung,heart and muscle were taken to determine the drug concentration.ResultsThe levels of ALT and AST in group CBATO and cTACE on 1,3 and 7 days after TACE were significantly higher than CB group(P <0.05)respectively.The ALT and AST levels in CBATO group were lower than cTACE group,but there was no statistical difference(P <0.05).There was no significant difference in the levels of BUN and Scr between the four experimental groups at each observation point.10 minutes and 20 minutes after TACE,the blood drug concentration of CBATO was significantly lower than cTACE(all P<0.001).The blood drug concentration of CBATO was lower than cTACE at 40 minutes,1,3 and 6 hours after TACE respectively,but the differences were not significant(all P>0.05).The blood drug concentration of CBATO was higher than cTACE at 12 hours,1 and 3 days after TACE respectively,but the differences were not significant(all P>0.05).In tumor tissue,the concentration of ATO in CBATO was higher than cTACE,and there was no difference in the 1 day after TACE,but there was a statistically difference between 3,7and 14 days(all P<0.05).Conclusion1.CalliSpheres drug-eluting beads(100-300μm)loaded with arsenic trioxide can prolong the time of drug metabolism,increase the drug concentration in tumor tissue and reduce the damage of liver and kidney function compared to lipiodol-arsenic trioxide emulsion2.At 1 days,3 days,7 days and 14 days after TACE,CalliSpheres drug-eluting beads(100-300μm)loaded with arsenic trioxide compared with lipiodol-arsenic trioxide emulsion,ATO concentration lower in kidney,lung,heart and muscle tissues.