锰苄基酪氨酸乙二胺四乙酸的肝靶向性及其在小鼠肝癌模型中的运用

The liver targeting of Mn-BnO-TyrEDTA and its preliminary application in a mouse liver cancer model

目的评价锰苄基酪氨酸乙二胺四乙酸(Mn-BnO-TyrEDTA)MRI对比剂的肝靶向性及其在小鼠肝癌模型上的初步运用。方法经尾静脉注射相同剂量的Mn-BnO-TyrEDTA和钆塞酸二钠(Gd-EOB-DTPA),并对小鼠进行MRI动态增强扫描,持续1 h,以监测对比剂的分布和清除情况。同时在小鼠肝脏上注射肝癌细胞H22(1×10^(5)/30μL)和基质胶(25μL)的混合液以建立肝癌模型,并对上述模型进行MRI。将钆喷葡胺作为对照组。结果注射Mn-BnO-TyrEDTA 1 min后肝脏开始强化,信号强度在3 min时达到峰值并持续至30 min;1 min后血液和肾脏信号强度开始明显降低,3 min后可见对比剂进入膀胱。通过比较3 min归一化信噪比和对比噪声比,判断两种对比剂肝靶向的强弱:Mn-BnO-TyrEDTA的归一化信噪比和对比噪声比分别为3.07±0.38和11±4.0,Gd-EOB-DTPA的归一化信噪比和对比噪声比分别为2.06±0.11和4.4±0.4,差异有统计学意义(P<0.05)。与正常肝实质比较,小鼠肝癌模型的肝内病灶呈明显低信号。结论Mn-BnO-TyrEDTA具有肝靶向性,并且经肝脏和肾脏双重途径清除,其在1~5 min的肝靶向性明显强于Gd-EOB-DTPA。小鼠肝癌模型的肝内病灶与周围正常肝实质具有较好的信号差异。

Objective To evaluate the liver targeting of manganese benzyltyrosine ethylenediamine tetraacetic acid(Mn-BnOTyrEDTA)MRI contrast agent and its preliminary application in mouse liver cancer model.Methods Mice were given by the same dose of Mn-BnO-TyrEDTA and disodium gadolinium serate(Gd-EOB-DTPA)via a caudal vein,and dynamic enhanced MRI scans were performed for 1 h to monitor the distribution and clearance of contrast agents.Simultaneously injecting liver cancer cell H22(1×10^(5)/30μL)into mouse liver and matrix adhesive(25μL)using a mixed solution to establish a liver cancer model and perform MRI imaging.Gd-DTPA was used as the control group.Results After injecting Mn-BnO-TyrEDTA for 1 min,the liver began to strengthen,and the signal intensity reached its peak at 3 min and continued until 30 min;After 1 min,the blood and kidney signal intensity began to significantly decrease,and after 3 min,the contrast agent entered the bladder.By comparing the normalized signal-to-noise ratio and contrast-to-noise ratio for 3 min,it was determined that the liver targeting values of the two contrast agents were 3.07±0.38 and 11±4.0 for Mn-BnO-TyrEDTA and 2.06±0.11 and 4.4±0.4 for Gd-EOB-DTPA,respectively,with statistical differences(P<0.05).Compared with normal liver parenchyma,the intrahepatic lesions in the mouse liver cancer model showed significantly low signal intensity.Conclusion Mn-BnO-TyrEDTA has liver targeting,and it is cleared through both liver and kidney pathways.Its liver targeting is significantly stronger than Gd-EOBDTPA at 1-5 min.There is a good signal difference between the intrahepatic lesions of the mouse liver cancer model and the surrounding normal liver parenchyma.