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

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Title: MR Imaging of activated hepatic stellate cells in liver injured by CCl4 of rats with integrin-targeted ultrasmall superparamagnetic iron oxide.
Authors: Wang QB (AUTHOR), Han Y (AUTHOR), Jiang TT (AUTHOR), Chai WM (AUTHOR), Chen KM (AUTHOR), Liu BY (AUTHOR), Wang LF (AUTHOR), Zhang C (AUTHOR), Wang DB (AUTHOR), Wang, Qing-Bing1 (AUTHOR), Han, Yu (AUTHOR), Jiang, Ting-Ting (AUTHOR), Chai, Wei-Min (AUTHOR), Chen, Ke-Min (AUTHOR), Liu, Bing-Ya (AUTHOR), Wang, Li-Fu (AUTHOR), Zhang, Chunfu (AUTHOR), Wang, Deng-Bin (AUTHOR)
Source: European Radiology. May2011, Vol. 21 Issue 5, p1016-1025. 10p.
Abstract: Objective: 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).Materials and Methods: 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.Results: 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.Conclusion: 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. [ABSTRACT FROM AUTHOR]
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Abstract:<bold>Objective: </bold>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).<bold>Materials and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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. [ABSTRACT FROM AUTHOR]
ISSN:09387994
DOI:10.1007/s00330-010-1988-z