胃癌新生血管靶向多功能探针在体MR和光学双模态成像的可行性  

In vivo dual-modality MR and near-infrared fluorescence imaging of gastric cancer neovasculature with targeted multi-functionalized nanoparticles

作　　者：康晓伟[1] 乔瑞瑞[2] 梁树辉[3] 吴开春[3] 刘先平[1] 印弘[1] 高明远[2] 魏光全[1] 

机构地区：[1]第四军医大学西京医院放射科,西安710032 [2]中国科学院化学研究所 [3]第四军医大学西京消化病医院肿瘤生物学国家重点实验室

出　　处：《中华放射学杂志》2014年第12期1038-1043,共6页Chinese Journal of Radiology

基　　金：国家自然科学基金（81071209,81090270）

摘　　要：目的 探讨胃癌新生血管靶向双模态分子探针在体MR和光学双模态成像的可行性.方法 将超顺磁性氧化铁纳米颗粒与Cy5.5-CX1耦联合成双模态分子探针DPs,测定探针的水合粒径和Zeta电位.取12只雄性裸鼠,建立胃腺癌皮下移植瘤模型.将12只鼠利用完全随机设计方法分为实验组与对照组,每组6只,分别通过尾静脉注射相同质量的DPs（实验组）和Fe3O4-Cy5.5（对照组）.于注射前及注射后4、8、12、18、24 h行T2WI,测量肿瘤内信号强度,计算对比噪声比（CNR）,并采用方差分析进行比较.选择2组肿瘤注射前及注射后（12 h）相同层面MR图像,计算信号降低百分比,并采用配对t检验进行比较.实验组和对照组鼠于注射药物后即刻及2、6、20、28、48 h行活体光学成像,观察体内的荧光分布.注射探针48 h后,处死各组实验鼠,分离皮下移植瘤及器官行离体荧光成像和病理检查.结果 常温下,Fe3O4-Cy5.5的平均水合粒径为（38.23±0.06）nm,平均Zeta电位为（0.29±0.16）mV;DPs的平均水合粒径为（39.49±0.16）nm,平均Zeta电位为（-4.15±0.79）mV.酶标仪检测偶联阳性率＞90％.实验组与对照组的肝、脾等网状吞噬系统MRI信号降低显著.实验组注射前及注射后4、8、12、18、24 h小鼠肿瘤的CNR分别为18.27±2.19、18.40±2.00、10.22±1.97、9.25±0.44、20.28±1.46和22.41±1.71,差异有统计学意义（F值=49.55,P＜0.01）,在注射探针后8、12 h CNR较注射前明显降低;对照组上述时间小鼠肿瘤的CNR分别为13.52±1.05、11.38±1.28、13.03±1.38、12.89±1.20、12.06±0.81和13.58±1.74,差异无统计学意义（F值=2.306,P＞0.05）.实验组肿瘤最外围信号降低百分比为（33.0±2.7）％,中央带为（22.0±1.6）％;对照组最外围信号降低百分比为（8.3±1.2）％,中央带为（3.8±0.9）％,2组肿瘤最外围的信号降低均比中央层显著,差异均有统计学意义（t值分别为-7.872和6.678,P均＜0.01）.�Objective To explore the feasibility of dual-modality probe to in vivo target angiogenesis of gastric cancer on MRI and near-infrared fluorescence （NIRF） optical imaging.Methods Cy5.5-GX1 with magnetic Fe3O4 nanoparticles were conjugated,resulting in dual-modality probe DPs.The hydrodynamic size and Zeta potential of DPs were analyzed by nano-ZS.Twelve male nude mice were obtained and established gastric adenocarcinoma subcutaneous transplantation tumor model.Twelve nude mice were divided into experimental group and control group （n=6 for each） by using completely random experimental design,then intravenously injected the same volume of DPs and Fe3O4-Cy5.5.MRI was applied before and 4,8,12,18,24 hours respectively after injections of nanoparticles to follow the changes of signals.For the evaluation of the MR images,the contrast to noise ratio （CNR） were calculated,and the different groups were compared with analysis of variance.MR images of the same level were selected before and 12 h after injections of nanoparticles in two groups and the percentage of reduced pixels was calculated,which were compared with the paired t test.At the same time,the time-resolved accumulation of the nanoparticles in the tumors were observed by using in vivo fluorescence imaging at 0,4,8,12,18,24 hours after injecting nanoparticles,respectively.Then tumor and normal tissues were collected,and ex vivo optical imaging and histopathology were performed on the tissues.Results At room temperature,the hydrodynamic size of Fe3Ox-Cy5.5 was （38.23±0.06） nm and the Zeta potential was （0.29±0.16） mV,and the hydrodynamic size of DPs was （39.49±0.16） nm and the Zeta potential was （-4.15±0.79） mV.The coupled rate of DPs with polypeptide was＞90％.The MRI signals of reticuloendothelial system were reduced significantly in experiment and control group.The tumor CNR of experiment group before and 4,8,12,18,24 h after injection were 18.27±2.19,18.40±2.00,10.22±1.97,9.25±0.44,20.28± 1.46 and 22.41 ± 1.71 （F=49.5

关 键 词：胃肿瘤 分子探针 磁共振成像 

分 类 号：R735.2[医药卫生—肿瘤] R445.2[医药卫生—临床医学]