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


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.


CONCLUSIONS
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.
Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qing-Bing
QB
Wang
Yu
Y
Han
Ting-Ting
TT
Jiang
Wei-Min
WM
Chai
Ke-Min
KM
Chen
Bing-Ya
BY
Liu
Li-Fu
LF
Wang
Chunfu
C
Zhang
Deng-Bin
DB
Wang
D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology*; D005295:Ferrocyanides / Q000494:pharmacology; D005355:Fibrosis / Q000473:pathology; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology*; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D008297:Male; D010455:Peptides / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005290:Ferric Compounds; D005295:Ferrocyanides; D039302:Integrin alphaVbeta3; D016023:Integrins; D010455:Peptides; C000499:ferric oxide; D002251:Carbon Tetrachloride; C000170:ferric ferrocyanide