不同粒径脂质体包裹顺磁性对比剂的体外R1弛豫率及MR增强成像研究

The Study of R1 Relaxivity and Enhanced MR Imaging Using Different Size of Liposomal Paramagnetic Contrast Agent

目的通过制备不同粒径脂质体包裹顺磁性Gd-DTPA,观察其理化特性及对大鼠肝脏的强化作用。材料与方法采用薄膜蒸发法制备不同粒径脂质体包裹顺磁性Gd-DTPA,观察其理化特性。动物实验选择雄性健康SD大鼠18只(平均分为3组),静脉注射不同粒径的顺磁性对比剂脂质体,于注射对比剂前、15min后对实验动物进行MRI。测定增强扫描前后肝脏、背景组织的信号强度,计算强化率、对比噪声比(CNR)。结果制备出粒径分别为400nm、200nm、78nm以下的顺磁性脂质体,其平均R1弛豫率分别为0.64、1.05、1.60mm-1.s-1,随着脂质体粒径减小,其包封率下降,体外R1弛豫率增高。静脉注射3种粒径的顺磁性脂质体后,肝脏的强化存在差异,表现为400nm粒径的脂质体对肝脏的强化作用高于其他2种粒径脂质体,测量肝脏的强化率和CNR较200nm、78nm脂质体差异有显著统计学意义(P<0.001)。结论脂质体包裹Gd-DTPA对肝脏具有强化作用,粒径大小对其弛豫率和强化作用有影响。

Objective To investigate characteristics of different size of liposomes encapculating Gd-DTPA,and their MR enhancement utility of liver. Materials and Methods The liposomes were prepared by hydrating a mixture with Gd-DTPA （Magnevist）.The liposomes were sized down to different diameters by extruder and exhaustively dialysed to remove unencapulated Gd-DTPA. The characterization of Gd-encapsulated liposomes was measured. In animal experiments,eighteen rats were divided into three groups. MR scan were performed before and at 15min after injection of different size of paramagnetic liposomal contrast agents. Enhancement percentage and contrast-to-noise ratio of liver were calculated and compared between groups. Results The in vitro R1 relaxivity of 400 nm,200 nm and 78 nm liposomes containing Gd-DTPA was 0.64,1.05,1.60 mm-1·s-1 respectively. For all size of liposomes,the smaller the liposome was,the greater the relaxivity and the lower the trapping efficiency were. The enhancement of liver caused by liposomal Gd-DTPA in diameter of 400 nm was greater than that of other two sizes of Gd-encapsulated liposomes. The enhancement percentage and CNR of liver after injection of 400 nm-liposomal Gd-DTPA were highest in three groups. Conclusion Gd-DTPA entrapped within liposome vesicles is effective relaxation agent. Both size of vesicles and lipid composition affect the relaxivity and liver enhancement.