DCE-MRI评估索拉非尼抑制兔VX2肝种植瘤血管生成的实验研究

摘要

目的:采用MR动态增强扫描成像(DCE-MRI)定量检测兔VX2肝种植瘤模型经索拉非尼靶向治疗前后的变化情况,探讨DCE-MRI进行疗效评估的可行性.方法:采用开腹瘤组织块包埋法制备兔VX2肝种植瘤模型,术后7天,通过MRI检查筛选形状规整、大小基本一致的VX2肝种植瘤实验兔30只,随机分为实验组和对照组(各15只),实验组经索拉非尼灌胃治疗,对照组采用同等剂量的5％葡萄糖灌胃治疗.实验兔分别于治疗前、治疗后7天、治疗后14天行DCE-MRI扫描,并记录肿瘤最大径线及定量参数Ktrans、Kep、Ve、Vp,最后一次扫描结束后,处死实验兔,行HE染色及微血管密度(MVD)、血管内皮生长因子(VEGF)免疫组化检查.结果:实验组与对照组之间Ktrans、Kep值差异有统计学意义(P＜0.05),Ve、Vp值差异无统计学意义(P＞0.05),Ktrans不同观察时间点的变化趋势不同,差异有统计学意义(P＜0.05).治疗14天后,两组间肿瘤直径增大值差异有统计学意义(P＜0.05).免疫组化分析显示两组间MVD、VEGF差异有统计学意义(P＜0.05).相关性分析结果显示Ktrans与MVD、VEGF之间呈正相关(r值分别为0.792和0.651),而其他定量参数与MVD、VEGF无明显相关性.结论:DCE-MRI可定量评估索拉非尼对兔VX2肝种植瘤抗血管生成的疗效.容积转移常数Ktrans与MVD、VEGF呈正相关,可反映治疗前后的微循环变化.%Objective:Using DCE-MRI parameters to quantitatively evaluate the response of sorafenib targeting treatment for implanted liver VX2 cancer at different time points before and after treatment,and to discuss the feasibility of DCE-MRI in the assessment of therapeutic effect.Methods:Rabbit VX2 liver cancer implantation model was established with tumor mass embedding method.7 days after tumor implantation,30 rabbit models with liver VX2 cancer that had the basically consistent shape and size were screened out through MRI.These rabbits were randomly divided into experimental group and control group (15 rabbits for each).In the experimental group,the rabbits were fed with sorafenib orally,while in the control group,the same amount of 5％ glucose was orally fed.DCE-MRI scan was performed before and on the 7th and 14th day after treatment.The maximum diameter of tumor and DCE-MRI parameters including microvascular Ktrans,Kep,Ve and Vp at the three time points were recorded.These rabbits were sacrificed afterwards,H&E staining and immunohistochemistry staining for micro vascular density and vascular epithelial growth factor (MVD,VEGF) were performed.Results:There were significant differences in Ktrans and Kep values between experimental and control groups (P＜0.05),yet no significant difference was existed in Ve as well as Vp value of the two groups (P＞0.05).At different observation time points,the trend of the Ktrans change showed significant difference (P＜0.05).Significant difference was existed in the maximum diameter of tumor between the two groups on the 14th day after treatment (P＜0.05),also in MVD and VEGF value between the two groups (P＜0.05).Positive correlation was showed between Ktrans value and MVD and VEGF result (r=0.792 and r=0.651,respectively).No correlation was found between other DCE-MRI parameters and MVD or VEGF.Conclusion:DCE-MRI parameters could be used to quantitatively evaluate the response of sorafenib treatment in the anti-vascular formation for rabbit VX2 liver implanted cancer.DCE-MRI parameter Ktrans has positive correlation with MVD and VEGF results,which is an important imaging biomarker to reflect microvascular changes before and after treatment.