Arterial Embolization Hyperthermia With Combination Of DSMA-Fe₃O₄Nano-sized Magnetic Fluid And Lipiodol In VX₂Hepatic Tumor Rabbit

PurposeThis experiment was to make arterial embolization hyperthermia withcombination of DSMA-Fe₃O₄（Fe₃O₄modified by dimercaptosuccinic acid）nano-sized magnetic fluid and Lipiodol in rabbit VX2carcinoma model, observed thesafety, feasibility and effectivity of the experiment, and explored the clinical potentialapplication.Materials and MethodsTwenty-five rabbits were implanted with VX2hepatic tumors into the left hepaticlobes.Then they were randomly divided into five groups and each group contained5rabbits. The five groups were Control group （A Group）, pure Lipiodol embolization（B Group），combination of DSMA-Fe₃O₄nano-sized magnetic fluid and Lipiodolembolization group （C Group）,DSMA-Fe₃O₄nano-sized magnetic fluidembolization hyperthermia group （D Group）,and combination of DSMA-Fe₃O₄nano-sized magnetic fluid and Lipiodol embolization hyperthermia group（E Group）.After two weeks, we did the plain and enhanced CT scan to observe the tumor shape,enhance performance, measured the volume of the tumor. Then, transarterialembolization was conducted with different emboliaztion agents which mentionedabove.Hyperthermia in alternating magnetic field were performed in Group D and Eafter embolization2days. After therapy7and14days， follow-up CT was performedto observe lipiodol deposition in the tumor distribution and tumor size, respectively, to calculate the tumor growth rate and tumor growth volume in all of subjects. Tumorgrowth rate was the ratio of the tumors’ volume at14th day after treatment to thetumors’ volume before treatment. The tumors’ volume before treatment subtractedfrom tumors’ volume7days and14days after treatment gave tumor growth volume.Some of each group were sacrificed after the last CT follow-up, and their whole liverswere removed for histopathology examination. Meanwhile，the function of liver of allthe subjects were measured1d before ernbolization and l,3and7day after therapyrespectively. Alanine aminotransferase（ALT） and aspartate aminotransaminase（AST）were used to reflect the function of liver. Tumor growth rates were analyzed by usingone-way analysis of variance （ANOVA）, the other data from every group wereanalyzed by using analysis of variance of repeated measure data.Results25VX2hepatic tumor rabbit models were successfully established and randomlydivide into five groups with5rabbits assigned to each group. The tumor volume at14days after VX2tumor implanted in group A, B, C, D, E, was （1856.3±438.2）mm3、（1826.9±346.0）mm3、（1886.6±403.2）mm3、（1896.3±226.4）mm3、（1953.4±494.8）mm3. There were no statistically significant differences among the five groups in thetumor volume.Interventional hepatic arterial catheterization were successfully performed in25animal models. On the14th day after treatment, the tumor volume in group E was（1435.4±346.3）mm3and tumor growth rate was73.7±3.0%，and the tumor sizedecreased by26.7%compared to that before treatment. However，On the14th dayafter treatment，the tumor volume in group B、C、D were （5375.4±549.5）mm3、（5741.5±1202.0）mm3、（9861.4±872.0）mm3and tumor growth rate were300.7±44.0%、309.4±50.1%、522.5±28.6%，respectively. And the tumor sizeincreased by200.7%、209.4%、422.5%compared to that before treatment， respectively.There were no statistically significant differences among the five groups in Both ALTand AST mean values. ALT in group A, B, C, D, E was [（30.0±5.9）U/L]、[（27.4±4.1）U/L]、[（29.2±4.8）U/L]、[（28.2±3.6）U/L]、[（28.4±4.1）U/L], and AST in groupA, B, C, D, E was [（36.8±4.9）U/L]、[（35.6±7.2）U/L]、[（33.5±4.6）U/L]、[（36.2±2.7）U/L]、[（37.9±4.5）U/L]。1and3days after treatment, B, C, D, E four groups of ALTand AST levels compared with before treatment were elevated and were statisticallysignificant （P <0.05）. In Group A, before treatment and1,3,7days aftertreatment,both ALT and AST levels were no statistically significant (F_ALT=1.981，P_ALT>0.05；F_AST=0.534，P_AST>0.05). Both ALT and AST7days after treatment7days compared with before treatmen, the difference was no statistically significant（P>0.05）.. Pathology: In Group A, the control group, the microscope showed significanttumor cell proliferation, big and deeply stained nuclear，and Abnormal split common.Group C, D, E were observed visible tan magnetic particles. Group E was not foundobvious tumor cells, replaced with inflammatory cells, and observed a large numberof fibrous connective tissue enveloping and the visible growth of granulation tissue.Group B, C were still found visibly the large nuclei and deeply stained tumor cells inperiphery, the central replaced by a large number of unstructured necrotic tissue, alsoobserved inflammatory reaction zone, inflammatory cells and fibrous connectivetissue. In Group D， it was still found the large number of tumor cells on theperiphery.ConclusionsArterial embolization hyperthermia with combination of DSMA-Fe₃O₄nano-sizedmagnetic fluid and Lipiodol in VX2hepatic tumor rabbit significantly improved thetumor necrosis rate. After therapy14days, the tumor volume reduced obviously. The damage to liver function temporary, the liver function could recover to the levelbefore the treatment.