Preliminary study of MR diffusion weighted imaging in nude mice models of hepatic Bel7402 tumors after adenovirus-mediated cytosine diaminase-thymidine kinase gene therapy

Abstract

Objective To study the characteristics of DWI in nude mice models of hepatic Bel7402 tumors after treatment with adenovirus-mediated cytosine diaminase-thymidine kinase ( Ad.CD-TK) double suicide gene therapy, and then to identify whether DWI can be used for assessing curative effect of postoperative tumors.Methods Thirty nude mice models of hepatic Be17402 tumors were successfully created using cell suspension method,after the tumor grew to more than 1 cm in diameter,20 tumor models were treated by intratumoral administration of Ad.CD-TK for 3 days plus intraperitonea( i.p.) treatment with 5-Fc and GCV for the duration of the study.Then they were randomly divided into three groups during 5-Fc and GCV treatment.The remaining 10 tumor models were used as controls.MR scanning were performed in 10th day before and after tumor implantation in all models by using EPI-SE series and SENSE technology for treatment group. Tumor volumes and ADC values were calculated pretreatment and posttreatment. Cell apoptosis were determined by using TUNEL method.Analyze the change of ADC and apoptosis index (AI) in different times,t test was used for comparison the difference of AI and ADC values respectively. Results After 10 days,the tumor volumes of the treatment groups and controls were respectively (724.16 ±57.45 ) mm3,( 754.57 ± 66.84 ) mm3,with no significant difference ( t =0.488,P ＞ 0.05 ).The ADC values of the treatment groups were (0.98 ±0.11 ) × 10-3 mm2/s,the ones of the control groups were (0.68 ±0.04) × 10 -3mm2/s;AI of the treatment groups were(23.25 ±6.57)％,the ones of the control groups were (2.57 ± 0.58) ％.There were difference in both groups ( t =4.473,5.874 ; P ＜ 0.01 ).Conclusion DWI can be effectively to monitor the early pathological changes of hepatic Bel7402 tumors after Ad.CD-TK double suicide gene therapy,and provide experimental evidences for clinical application. Key words: Liver neoplasms ; Magnetic resonance imaging; Comparative study