| OBJECTIVE:To explore the feasibility and application of brachytherapy for VX2 liver tumor using elastin-like polypeptides as carrier with 131 I so as to provde the reliable experimental evidences for a new promising treatment method of liver cancer. METHODS:(1) Establish the model of VX2 liver tumor in New Zealand white rabbit 20 male healthy New Zealand white rabbits implanted VX2 liver tumor by tissue fragment method were selected for the research. The tumor growth was monitored by B ultrasonic examination and the changes of liver function(ALT, AST and TBil) were analyzed. The weight, spontaneous survival time and histopathological changes of the animal were observed.(2) Elastin-like polypeptides as carrier was labeled with 131 I Elastin-like polypeptides was labeled with 131 I by Iodogen method. The labeling efficiency, radiochemical purity and the stability in vitro of 131I-ELP after purification were detected by isotope thin-layer chromatography(i-TLC).(3) Brachytherapy using 131I-ELP for VX2 liver tumor 10 VX2 liver tumor models with approximate 1 cm of tumor diameter but no internal liquefaction and necrosis were randomly divided into the treatment group(n=5) and the control group(n=5). In the treatment group, 1ml 131I-ELP by ultrasound guided was injected into VX2 liver tumor internal for brachytherapy. SPECT/CT imaging of was performed after injection of 131I-ELP to observe tumor growth and tissue distribution of radioactive iodine 131. In the control group, 1ml ELP by ultrasound guided was injected into VX2 liver tumor. CT imaging was performed after injection of ELP to observe tumor growth. At the same time, detected the content of ALT, AST and observed the spontaneous survival time and histopathological changes in the treatment group and the control group. RESULTS:(1) 18 rabbits were found liver tumors growth. The successful rate of implantation liver tumors was 90%. B ultrasonic examination showed the liver tumors presented as nodular low echo with clear border and rich blood supply. On 7 day, 14 day and 21 day after the implanting, the tumors diameter could grow up to 0.57 ± 0.09 cm, 1.14 ± 0.30 cm, 2.73 ± 0.40 cm respectively. On the 14 days and 21 days after the implanting, the ALT level and AST level showed significantly higher than before the procedure respectively(P<0.05).While on the 7 days, 14 days, 21 days after the procedure and before the implanting, the TBil level has no statistically significant differences between each group(P>0.05). The spontaneous survival time of VX2 liver tumor rabbits was 37.90±14.31 days. The cachexia occurred on the 35 days after the implanting. Macroscopic observation showed the tumors were white in color, hard in texture and tofu-dreg necrosis in the internal. Histopathological examination showed a large number of tumor cells were markedly necrosed in the center of VX2 liver tumor, tumor cells in the periphery were arranged in disorder with obvious nuclear atypia with no uniform size, and the boundary between tumor tissue and liver parenchyma was obscure.(2) The paper chromatography by i-TLC indicated that the labeling efficiency and radiochemical purity of 131I-ELP were 73.9% and 99.3% respectively. The stability of 131I-ELP in vitro was maintained over 96.8% in 96 h.(3) SPECT/CT imaging found radioactivity 131 I was specifically localized in VX2 liver tumor with stationary, lasting and confined. The differences of the ALT and AST level respectively on the 7 days and 14 days after the procedure were statistically significant between the treatment group and the control group(P<0.05). There were no significant differences in survival time between the treatment group and the control group( t=2.026, P=0.077).Histopathological examination showed the treatment group presented a large number of tumor cells marked necrosis, obvious fibroplasia and inflammatory cell infiltration. The major organs of liver surround found no fibroplasia and inflammatory cell infiltration. CONCLUTIONS: 1. The VX2 rabbit model of liver tumor by tissue fragment method may be developed as a suitable and ideal platform to test brachytherapy for liver cancer. 2. ELP as ideal carrier with 131 I has thermally sensitive, good tissue compatibility injectable and biodegradable advantages. 131I-ELP can be easily labeled by Iodogen method with high labeling efficiency, radiochemical purity and stability. 3. Brachytherapy using 131I-ELP for liver tumor is a useful method which can improve liver function and inhibit tumor growth, with lower toxicity and higher antitumor efficacy advantages. |
PDF Full Text Request