MR Imaging of activated hepatic stellate cells in liver injured by CCl4 of rats with integrin-targeted ultrasmall superparamagnetic iron oxide

作者：Wang, Qing-Bing; Han, Yu; Jiang, Ting-Ting; Chai, Wei-Min; Chen, Ke-Min; Liu, Bing-Ya; Wang, Li-Fu; Zhang, Chunfu; Wang, Deng-Bin^*

来源：European Radiology, 2011, 21(5): 1016-1025.

DOI：10.1007/s00330-010-1988-z

• Magnetic resonance imaging
• Iron oxide particles
• Cellular targeting imaging
• Hepatic stellate cell
• Liver injury
• Ultrasmall superparamagnetic iron oxide
• Integrin
• c(RGDyC) peptide

To demonstrate the feasibility of the ultrasmall superparamagnetic iron oxide (USPIO) modified by cyclo (Arg-Gly-Asp-Try-Cys) peptide (c(RGDyC)-USPIO) for targeting hepatic stellate cells (HSCs).
A c(RGDyC)-USPIO probe was prepared by conjugating c(RGDyC) with USPIO through a thiol-maleinide interaction. The specificity of c(RGDyC)-USPIO for HSCs was investigated in vitro. In vivo, normal and fibrosis rats were treated with either c(RGDyC)-USPIO or USPIO, and magnetic resonance imaging (MRI) of the rats performed after administration of the probes for 4 h. The T2 relaxation times changes before and after probe injection were analyzed and the locations of probes in normal or injured mice were identified histologically.
The hydrodynamic size of c(RGDyC)-USPIO was 13 +/- 3 nm. HSCs took up more specific probes than plain ones. The reduction of T2 relaxation times in fibrosis rat by c(RGDyC)-USPIO was much greater than that by USPIO (P < 0.05). Prussian blue staining and transmission electron microscopy of the injured rat liver treated with c(RGDyC) demonstrated that c(RGDyC)-USPIO were specifically engulfed by the activated HSCs.
In vivo cellular targeted imaging of activated HSCs in liver fibrosis using c(RGDyC)-USPIO targeting alpha(v)beta(3) integrins was feasible using a clinical 1.5-Tesla MR system.

• 出版日期2011-5
• 单位上海市闵行区中心医院; 上海交通大学