磁共振T2对比剂Fe3O4@Cys的制备及新西兰兔活体成像研究  

Preparation of magnetic resonance T2 contrast agent Fe3O4@Cys and live imaging study of New Zealand rabbits

作　　者：祖涵瑜 陈梦莎 韩慧婷 闫鹏 陈亮[1] 黄娅楠 张濬韬 姜兴岳[1] ZU Hanyu;CHEN Mengsha;HAN Huiting;YAN Peng;CHEN Liang;HUANG Yanan;ZHANG Juntao;JIANG Xingyue(Department of Radiology,Affiliated Hospital of Binzhou Medical University,Binzhou 256600,China;Basic Medical College,Binzhou Medical University,Yantai 264003,China;GE Healthcare Shanghai Co.,Ltd.,Shanghai 201203,China)

机构地区：[1]滨州医学院附属医院放射科,滨州256600 [2]滨州医学院基础医学院,烟台264003 [3]通用电气药业(上海)有限公司,上海201203

出　　处：《磁共振成像》2023年第10期105-110,共6页Chinese Journal of Magnetic Resonance Imaging

基　　金：国家自然科学基金项目(编号:51401031);山东省自然科学基金项目(编号:ZR2018LH015)。

摘　　要：目的 制备经半胱氨酸(cysteine, Cys)表面修饰的磁共振T2对比剂Fe_(3)O_(4)@Cys,并通过3.0 T磁共振成像系统经新西兰兔测试其成像性能。材料与方法 采用溶剂热法,通过改变反应时间和底物浓度,制备出不同的Fe_(3)O_(4)纳米颗粒。采用X射线衍射仪对样品进行表征并分析其结晶性,经扫描电子显微镜测试其形貌及粒径,选择结晶性较高且粒径均匀的样品进行Cys表面修饰,经ZETA电位纳米粒度分析仪测得Fe_(3)O_(4)、Fe_(3)O_(4)@Cys的表面电位,经震动样品磁强计对其进行磁性能测试,经MTT法细胞增殖抑制实验测试样品修饰前后的细胞毒性。使用3.0 T磁共振成像系统,通过观察新西兰兔注射前后不同时间点肾脏皮质、髓质及小肠的信号变化,测试其成像性能。结果 当FeCl3·6H2O的用量选择0.325 g,200℃温度下反应8 h所制备的Fe_(3)O_(4)纳米颗粒结晶性高,平均粒径约57.2 nm,修饰前后表面电位分别为-20 mV与-22 mV,扫描电镜下粒径及形貌未发生明显改变,修饰后不同浓度Fe_(3)O_(4)@Cys的24 h细胞存活率均高于80%,且均高于Fe_(3)O_(4)组。修饰后Fe_(3)O_(4)纳米颗粒表现出超顺磁性,在磁共振活体成像中具有明显的阴性对比增强效果。结论 反应时间延长,Fe_(3)O_(4)结晶性增加;底物浓度增加,Fe_(3)O_(4)粒径减小。Cys修饰后,稳定性与生物相容性增加,可作为T2对比剂用于多种实验和基础研究。Objective:To prepare the magnetic resonance T2 contrast Fe_(3)O_(4)@Cys modified with cysteine(Cys)surface and tested by New Zealand rabbits using a 3.0 T magnetic resonance imaging system.Materials and Methods:Using the solvent thermal method,different Fe_(3)O_(4) nanoparticles were prepared by changing the reaction time and substrate concentration.The samples were characterized by X-ray diffractometer and their crystallinity were analyzed.The morphology and particle size of the samples were measured by scanning electron microscope.The samples with high crystallinity and uniform particle size were selected for surface modification with Cys.The surface potentials of Fe_(3)O_(4),Fe_(3)O_(4)@Cys were measured by ZETA Potential Nanoparticle analyzer.The magnetic properties of Fe_(3)O_(4) and Fe_(3)O_(4)@Cys were tested by vibration sample magnetometer.The cytotoxicity of the samples before and after modification was tested by MTT cell proliferation inhibition assay.The imaging performance was tested by observing signal changes in the renal cortex,medulla and small intestine at different time points before and after injection.Results:When the amount of ferric chloride hexahydrate was 0.325 g,the Fe_(3)O_(4) nanoparticles prepared for reaction at 200℃temperature had high crystallization and uniform particle size.The average particle size was about 57.2 nm,the surface potential was-20 mV and-22 mV respectively.The particle size and morphology were not significantly changed,and the cell survival rate of Fe_(3)O_(4)@Cys was higher than 80%,which was higher than that of Fe_(3)O_(4) group.The modified Fe_(3)O_(4) nanoparticles exhibit superparamagnetism and have obvious negative contrast enhancement effect in magnetic resonance imaging in vivo.Conclusions:As the reaction time increases,Fe_(3)O_(4) crystallization increases;substrate concentration increases and Fe_(3)O_(4) particle size decreases.Cys modification increases stability with biocompatibility and can be used as a T2 contrast agent for a variety of experimental

关 键 词：分子影像 四氧化三铁 对比剂 纳米材料 磁共振成像 

分 类 号：R445.2[医药卫生—影像医学与核医学] R-332[医药卫生—诊断学]