摘要
在大鼠Walker-256移植性肝脏肿瘤模型上采用磁共振影像检测结合病理诊断,建立血管阻断药物的临床前研究方法,并用血管阻断药物考布他汀A4磷酸酯(CA4P)验证该方法的可靠性。20只SD大鼠左肝包膜下制成Walker-256移植性肝脏肿瘤模型,采用1.5T磁共振仪行T1WI、T2WI、DWI、CE-T1WI检查;CA4P治疗后24,48,72h采用以上序列再次进行MRI检查。扫描结束后处死动物,取肝脏肿瘤组织部位进行病理组织学检查。结果显示,与正常肝脏比较,肿瘤在T1WI图像上呈略低信号,T2WI呈高信号,DWI呈亮高信号,CE-T1WI呈略高信号。CA4P治疗后CE-T1WI中央区域低信号,边缘高信号,信号强度增强率降低(P<0.01),肿瘤体积增长明显小于对照组(P<0.01),坏死面积比率增大(P<0.01)。病理检查显示,对照组肿瘤血管内皮细胞扁平,血管内无栓塞;CA4P治疗后,可见肿瘤内大范围的坏死和血栓,血管内皮细胞肿胀。实验结果表明,MRI可以准确、无创性评价CA4P对大鼠Walker-256移植性肝脏肿瘤的疗效。应用1.5TMRI结合病理学检查方法可以作为血管阻断药物的临床前疗效研究方法。
The study was to establish a preclinical assessment method for vascular disrupting agents in rat liver tumor model of Walker-256 using magnetic resonance imaging（MRI） in correlation with histology and combretastatin A-4-phosphate（CA4P） to verify the reliability of the method.Twenty tumors of 10×10 mm in diameter were obtained 16 days after implantation in left liver lobes of 20 rats.Using a 1.5T MR set,T2-weighted imaging（T2WI）,pre-and post-contrast T1-weighted imaging（T1WI）,diffusion-weighted imaging（DWI） were acquired at baseline,24 hour,48 hour and 72 hour after iv injection of CA4P at 10 mg/kg and vehicle in treated and control rats,respectively.Rats were sacrified after the MRI scanning and their tumors were dissected for histopathological analysis.The results showed that,relative to normal liver,the tumors appeared to be hypo-intense on T1WI,hype-rintense on T2WI,strongly hyper-intense on DWI and was enhanced with a clear border on CE-T1WI.On CE-T1WI,CA4P-treated tumors were hypo-intense in the central region relative to peripheral enhanced tumor.The tumors in CA4P-treated group showed slower growth（P0.01）,decreased signal intensity enhancement ratio（ER）（P0.01） and increased tumor necrosis ratio（P0.01） compared with the control group respectively.Histopathological findings showed that untreated liver masses were composed of viable tumor cells with tumoral endothelium in flat shape and without vascular thrombosis.After the treatment,Massive central necrosis and stable thrombus occurred in the tumor.The findings indicate that MRI can accurately and non-invasively reflect the therapeutic effect of CA4P on rat liver tumor.A clinical 1.5T MRI scanner with histopathology can be used as a preclinical assessment method for analyzing therapeutic effects of vascular disrupting agents.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2010年第6期558-562,共5页
Journal of China Pharmaceutical University
基金
江苏省国际合作项目资助(No.BZ2009097)
浙江省教育厅资助项目(No.Y20090801)~~
