Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Eur Radiol. 2011 May;21(5):1016-25. doi: 10.1007/s00330-010-1988-z. Epub 2010 Oct 25.
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 α(v)β(3) integrins was feasible using a clinical 1.5-Tesla MR system.
展示经环（精氨酸-甘氨酸-天冬氨酸-半胱氨酸）肽（c（RGDyC）-超顺磁性氧化铁（USPIO））修饰的超小超顺磁性氧化铁（USPIO）用于靶向肝星状细胞（HSCs）的可行性。
通过巯基-马来酰亚胺相互作用将 c（RGDyC）与 USPIO 缀合，制备 c（RGDyC）-USPIO 探针。在体外研究 c（RGDyC）-USPIO 对 HSCs 的特异性。在体内，正常和纤维化大鼠分别用 c（RGDyC）-USPIO 或 USPIO 处理，并在给予探针后 4 小时对大鼠进行磁共振成像（MRI）。分析探针注射前后 T2 弛豫时间的变化，并通过组织学鉴定探针在正常或受损小鼠中的位置。
c（RGDyC）-USPIO 的水动力粒径为 13±3nm。HSCs 摄取的特异性探针多于普通探针。c（RGDyC）-USPIO 使纤维化大鼠 T2 弛豫时间的减少明显大于 USPIO（P<0.05）。用 c（RGDyC）处理受损大鼠的肝脏普鲁士蓝染色和透射电镜显示，c（RGDyC）-USPIO 被活化的 HSCs 特异性吞噬。
使用靶向α（v）β（3）整合素的 c（RGDyC）-USPIO 对肝纤维化中活化的 HSCs 进行体内细胞靶向成像，在临床 1.5T MR 系统中是可行的。
