ABSTRACT
To investigate the value of the total liver CT perfusion imaging in the evaluation of rabbit VX2 liver tumors treated with TACE and apatinib. Methods: Thirty-six rabbit VX2 liver cancer models were established and randomly divided into 4 groups. Group A: simple TACE group; Group B: simple oral administration of apatinib mesylate; Group C: TACE + oral apatinib mesylate; Group D: control group, administration of saline. CT perfusion imaging (CTPI) was performed before treatment and on the 7 and 14 days after the treatment to acquire perfusion parameters including blood flow (BF), blood volume (BV), MTT (mean transit time), surface permeability (PS), and hepatic artery fraction (HAF). One tumor rabbit was sacrificed in each group after the first perfusion scan, and the remaining tumor rabbits were sacrificed after the last perfusion scan on the 14th day of the treatment. The borders of the tumors were stained immunohistochemically, and microvascular density (MVD) was measured by anti-CD34. The differences of perfusion parameters were compared to evaluate the liver hemodynamic changes, and statistical repeated measurement variance analysist correlation analysis were performed. Results: There were no significant differences in CTPI parameters of BF, BV, MTT, HAF and PS between the 4 groups before treatment (P>0.05). After the treatment, HB, HAF and PS were decreased significantly in Group A, B, and C and slightly increased in the Group D. The value of MVD after 14 d treatment was 80.1±16.4 in Group A, 50.2±11.2 in Group B, 27.4±9.7 in Group C, 68.7±12.7 in Group D, respectively. The value of MVD in the Group C were significantly lower than that in Group A, B, and D. It showed positive correlation between BF, HAF, PS and MVD in Group B, C, and D, and there was no significant correlation between BV, MTT and MVD. It showed no significant correlation between MVD and each CTPI parameter in Group A. Conclusion: Total liver CT perfusion can quantitatively evaluate the blood perfusion information of rabbit liver VX2 tumor after TACE. TACE combined with oral apatinib can effectively inhibit tumor growth and improve the therapeutic effect of VX2 tumor.
Subject(s)
Animals , Rabbits , Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Neovascularization, Pathologic , Perfusion Imaging , Pyridines , Tomography, X-Ray ComputedABSTRACT
Objective:To evaluate the feasibility and therapeutic efficacy of transhepatic arterial embolization with superparamagnetic iron oxide (SPIO) and lipiodol (LIP) for the treatment of VX2 tumor in rabbits.Methods:Twenty-four rabbits with hepatic VX2 tumors by surgical implantation were randomly divided into 4 groups and treated with transhepatic arterial embolization of 4 different agents as follows (n=6 each):doxorubicin (DOX) group,DOX-LIP group,SPIO-DOX group,and SPIO-DOX-LIP group.Liver function (AST and ALT) was measured at 0,1,3,5 and 7 d after transhepatic arterial embolization.The serum DOX level was measured at 0,5,15,30,60,and 120 minutes after transhepatic arterial embolization.MRI was performed at 7 d after the treatment to assess the distribution of SPIO in the SPIO-DOX group and SPIO-DOX-LIP group,while CT was performed to assess the distribution of LIP in the DOX-LIP group and SPIO-DOX-LIP group.All the rabbits were sacrificed and their livers were removed at 7 d after treatment for the detection of tissue DOX level.The histopathologic examinations were performed including HE staining,Prussian blue staining and TUNEL assay,and then the tumor necrosis percentage and apoptosis index were calculated.Results:Compared to the DOX group,the levels of AST and ALT in other 3 groups were significantly elevated at 1 and 3 d after embolization (P＜0.05).The levels of ALT and AST in the DOX group,DOX-LIP group or SPIO-DOX-LIP group returned to the baseline at day 7,there were no significant differences (P＞0.05).The SPIO-DOX-LIP group exhibited the lowest serum DOX level at all time points up to 120 minutes after embolization (P＜0.05).However,the tissue DOX level in the SPIO-DOX-LIP group was the highest among all groups at day 7 (P＜0.05).The SPIO-DOX group and SPIO-DOX-LIP group showed significantly lower MRI signal intensity of tumors in T2 weighted imaging (T2WI) at day 7.Meanwhile DOX-LIP group and SPIO-DOX-LIP group showed that high-density lipiodol was deposited in the tumors in CT images.Histopathologic findings showed an almost complete central necrosis coagulation of tumors in the SPIO-DOX-LIP group,and the tumor necrosis percentage and tumor apoptosis index were significantly increased in the SPIO-DOX-LIP group compared to those in other 3 groups (P＜0.05).Conclusion:This novel drug-delivery system of SPIO nano-drug carrier together with LIP is safe and feasible when it is used for transhepatic arterial embolization for liver tumor.It provides an excellent MR and CT visualization and improves the therapeutic efficacy for the treatment of rabbit VX2 liver tumor.