| Objective To explore the efficacy of 131 I – ELP in the treatment of VX2 liver tumor by brachytherapy,and to evaluate the therapeutic effect of 131 I – ELP with different radioactive concentrations on liver cancer,so as to discover a novel promising therapeutic modalities of liver cancer.Its safety and feasibility will be evaluated,to provide reliable experimental evidence for clinical application.Methods1.Establishment of the VX2 liver tumor models:VX2 liver tumors were implanted to the rabbits by block embedded tumor tissues.Sonography was performed to monitor the growth of liver tumors by the same doctor each time.2.Preparation for different radioactive concentrations of 131 I – ELP :Elastin-like polypeptides were labeled with 131 I using the iodogen oxidative reaction method,and then the reaction products were purified by centrifugal ultrafiltration.The radiochemical purity of 131 I – ELP with desired radioactive concentration(50 m Ci/m L or 100 m Ci/m L)was monitored with isotope paper chromatography to assess the stability in vitro.3.Brachytherapy using 131 I – ELP for VX2 liver tumor:The rabbits with VX2 liver tumor were randomly divided into three groups,two therapy groups and a control group.131 I – ELP with different radioactive concentrations and ELP were injected into the VX2 liver tumors separately.Imaging surveillance and biochemical tests of liver function and blood count were required to assess treatment efficacy.Animals were sacrificed 2 weeks post-treatment to observe the necrotic rate of tumors and histopathological changes.Results 1.Twenty-four rabbits have remained alive with liver tumors growth.On days 14 after implantation,the images of VX2 liver tumors showed the maximum diameters were 1.43 ± 0.37 cm and the volumes were 0.78 ± 0.44 cm3.2.The result of isotope paper chromatography indicated that the stability of 131I-ELP in vitro was maintained 99.0%?98.9%?98.6%?97.9% and 97.3%,respectively,as it was incubated on ice for 0h?24h?48h?72h?96h.3.SPECT/CT imaging showed that the radionuclides were specifically localized in VX2 liver tumor at days 7 and 14 after injection of 131 I – ELP.Imaging indicated brachytherapy using 131 I – ELP for VX2 liver tumor can inhibit tumor growth(P < 0.05),and the TGR of 100 m Ci/m L 131 I – ELP group was significantly lower than the 50 m Ci/m L 131 I – ELP group(P < 0.05).With the different radioactive concentrations of 131 I – ELP injected into the VX2 liver cancer in rabbits could improve the liver function,and in AST level at days 7,more obvious changes of 50 m Ci/m L 131 I – ELP group compared with 100 m Ci/m L 131 I – ELP group(P < 0.05).The differences of the ALT level at days 7 and 14 were not statistically significant between the two treatment groups,similar results were found in the AST level at days 14(P > 0.05).Compared with control group,treatment groups have significant leukocytosis at 7 and 14 days after therapy(P < 0.05).But the effects were not obvious in the level of RBC and Hb(P > 0.05).Additionally,significant difference in the necrotic rate existed among the three groups.For the 100 m Ci/m L 131 I – ELP group,the necrotic rate of tumor was highest,and the necrotic rate of ELP group was lowest.The pathology result of 100 m Ci/m L 131 I – ELP group showed distension was found in hepatic sinusoid and portal bile duct,and funicular fiber hyperplasia in adjacent normal tissue.No radiation-induce injuries of normal hepatic tissue was observed in 50 m Ci/m L 131 I – ELP group.Conclutions1.The rabbit VX2 model of liver tumor by block embedded tumor tissues method is reproducible and simple,and gives a high rate of positivity.The rabbit VX2 model of liver tumor may be an ideal and suitable animal model for subsequent brachytherapy.2.ELP can be an ideal carrier for 131 I and have high radiochemical purity and stability.3.Brachytherapy with 131 I – ELP for liver tumor has better outcomes in tumor suppression and improving liver test results,and freedom from side effects including bone marrow depression and radiopharmaceutical migration.100 m Ci/m L 131 I – ELP group has more effect in tumor suppression than 50 m Ci/m L 131 I – ELP group,while this group also could injure much more surrounding normal liver tissue. |
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