磁共振R2*mapping示踪功能型纳米药物载体在NSCLC裸鼠模型的显像研究

The Preliminary Application of Functional Drug-Loaded Nanosystem in the Field of NSCLC-bearing Mice with MR R2*Mapping Technique

目的通过磁共振R2*mapping技术示踪及动态监测NSCLC裸鼠模型给药后不同时间点R2*值的变化趋势,阐明R2*mapping在评价F/A-PLGA@DOX/SPIO纳米载药体系在肿瘤成像中的应用价值及影像学基础。方法成功构建NSCLC裸鼠移植瘤模型24只,随机分为G1、G2两组,每组12只。分别尾静脉注射单纯SPIO以及F/A-PLGA@DOX/SPIO纳米载药体系,并采用1.5 T MR和动物专用小鼠线圈对建模成功荷瘤裸鼠皮下移植瘤模型进行R2*扫描获得肿瘤区域R2*值。实验结束后全部肿瘤组织及肝脏、脾脏普鲁士蓝染色。结果G2组每个时间点的R2*值均高于G1组(P<0.05)。相对于G1组,G2组肿瘤R2*值在早期上升趋势明显,且在给药后60h时明显高于G1组(P<0.05)。G1组排泄期较G2组明显提前。普鲁士蓝染色结果显示,G2组肿瘤的蓝色铁沉积高于SPIO组,而肝脏、脾脏组织的蓝色铁沉积低于G1。结论R2*值与肿瘤组织内的SPIO含量存在较高敏感性,R2*mapping技术提供了一种SPIO的肿瘤示踪成像方法。

Objective MR R2*mapping is used to trace and dynamically monitor the changing trend of R2*value of NSCLC-bearing mice at different time points after administration to elucidate the application value and imaging basis of R2*mapping in the noninvasive evaluation of F/A-PLGA@DOX/SPIO nanosystem in tumor imaging.Methods The nude mice A549 subcutaneous transplantation model was built.We selected 24 tumor-bearing mice,dividing them into two groups,with 12 in each group.The two groups were injected with SPIO and F/A-PLGA@DOX/SPIO,respectively.We used GE Healthcare 1.5 T clinical MRI and animal-specific mouse coils to conduct R2*mappingon the subcutaneously implanted tumor model to obtaine the R2*value of the tumor area.After MR scanning,all their tumor tissue,liverand spleen were removed and Prussian blue stained.Results The R2*value G2 at each time point was higher than G1(P<0.05).Compared to G1,the R2*value of tumors of G2 increased significantly at the early stage,the R2*value was significantly higher than that of G1 at 60 hours(P<0.05).The excretory phase of G1 was significantly earlier than that of the targeted contrast agent group.Prussian blue staining:the blue iron deposit of tumor tissue in G2 was higher than that in G1,while blue iron deposits in liver and spleen tissues were lower than in G1.Conclusion R2*value is highly sensitive to SPIO content in tumor tissue.R2*imaging sequence provides a imaging method for tumor imaging to trace SPIO.