In vivo evaluation of a monodisperse solid-in-oil-in-water miriplatin/ lipiodol emulsion in transcatheter arterial chemoembolization using a rabbit VX2 tumor model

摘要

Transcatheter arterial chemoembolization (TACE) is a standard treatment for unresectable hepatocellular carcinoma; however, it does not always result in tumor control. Nevertheless, treatment outcome can be improved with monodisperse emulsions of anticancer agents. In this study, the distribution of a monodisperse miriplatin-Lipiodol emulsion in the tumor and its safety were evaluated in ten Japanese white rabbits. VX2 tumor was implanted into the left liver lobe. The animals were divided into control and experimental groups (of five animals each) and respectively administered a conventional miriplatin suspension or the emulsion via the left hepatic artery. Computed tomography (CT) was performed before, immediately after, and two days following TACE. All rabbits were sacrificed two days after the procedure. Each tumor was removed and cut in half for assessment of iodine concentration in one half by mass spectroscopy and evaluation of Lipiodol accumulation and adverse events in the other half. Mean Hounsfield unit (HU) values were measured using plain CT images taken before and after TACE. Iodine concentration was higher in the experimental group [1100 (750–1500) ppm, median (range)] than in the control group [840 (660–1800) ppm], although statistically not significant. Additionally, the HU value for the experimental group was higher than that for the control group immediately after [199.6 (134.0–301.7) vs. 165.3 (131.4–280.5)] and two days after [114.2 (56.1–229.8) vs. 58.3 (42.9–132.5)] TACE, although statistically not significant. Cholecystitis was observed in one rabbit in the control group. Ischemic bile duct injury was not observed in any group. The results show that Lipiodol accumulation and retention in VX2 tumor can possibly be improved with a monodisperse emulsion; however, it should be verified with a larger study. Moreover, no significant adverse events are associated with the use of the emulsion.