目的 制备一种小粒径磁共振成像(MRI)超敏感的纳米对比剂并进行初步动物实验,探讨其用于分子影像学研究的可行性.方法 利用聚乙二醇(PEG)引发ε-己内酯(CL)开环聚合与自组装技术制备嵌段聚合物PEG-b-PCL,在其疏水性内核负载单颗粒超顺磁性氧化铁(SPIO)制成纳米对比剂.应用透射电子显微镜测量该纳米对比剂的粒径,原子吸收法测量其SPIO负载率,多平面回波SE序列测量T2值并计算横向弛豫率R2,同时对其进行磁学性质测量.将纳米对比剂由鼠尾静脉注射入Balb/c裸鼠体内,利用MRI于注射前、注射后1、3、6、12、24 h共6个时间点进行扫描,观察其在裸鼠体内的分布特点及循环时间.结果 制备的纳米对比剂粒径为(38±3)am,Fe3O4含量为37.0%,横向弛豫率R2为110 Fe(mmol/L)-1·s-1;磁学性质测定结果表明其具有超顺磁性.经外周静脉注射后,主要分布于肝脏,且循环时间长,与注射前相比,1 h信号强度明显降低(498±60比120±32,P<0.05),至24 h降低至88+28(P<0.05).结论 负载单颗粒SPIO的聚合物纳米对比剂粒径小、MRI超敏感,具有成为MRI对比剂并用于分子靶向成像的潜能.
Objective To synthesize a small size and super-sensitive magnetic resonance imaging (MRI) nano-contrast agent for preliminary animal experiment and to explore the feasibility for its use in molecular imaging studies.Methods Polyethylene glycol (PEC) was used for ring-opening polymerization of ε-caprolactone(CL), and amphiphilic PEG-b-PCL block polymer was prepared by self-assembly technique.Single particle superparamagnetic iron oxide (SPIO) was loaded at the hydrophobic core of PEG-b-PCL to develop a nano-contrast agent.The particle diameter and SPIO-loading density were respectively determined by transmission electron microscope and atomic absorption spectroscopy.Echo multiplanar sequence was used for T2 value test, with transverse relaxation rate R2 computed.Meanwhile, magnetic properties were tested.After intravenous injection via caudal vein of Balb/c nude mice, the distributions and circulation time of this nano- particle were analyzed using MRI scanner at before injection and lh, 3h, 6 h, 12 h and 24 h after injection.Results The micelle diameter was around (38+3) nm and the content of Fe3O4 (wt%) was 37.0%.The transverse relaxation rate R2 was 110 Fe(mmol/L)-1 ·s-1.Superparamagnetism was observed in magnetic property test.After intravenous injection, the nano-particles were mainly distributed in the liver with a long circulation time.Signal intensity at 1 h decreased significantly when compared with that of before injection (120±32 vs 4986±0, P<0.05) , and then decreased to (88±28) at 24 h (P<0.05).Conclusion The nanometer micelle loaded with single SPIO particle demonstrates its potential as a powerful MRI contrast agent for molecular imaging studies because of its small size and high sensitivity.