Molecular MRI of activated hepatic stellate cells in rats with early stage of liver fibrosis by targeting hepatic integrin α5β1

Objective: To investigate the feasibility of ultrasmall superparamagnetic iron oxide (USPIO) modified by anti-alpha 5 beta 1 integrin monoclonal antibody (mAb) for targeting activated hepatic stellate cells (HSCs) in early stage of hepatic fibrosis rats in vivo. Methods: The early stage hepatic fibrosis model of rats was established by injecting carbon tetrachloride subcutaneously. The anti-alpha 5 beta 1 integrin mAb-USPIO probe was prepared by conjugating anti-alpha 5 beta 1 integrin mAb with USPIO through carbodiimide method. Four normal rats were treated with anti-alpha 5 beta 1 integrin mAbUSPIO as control group. Twelve hepatic fibrosis rats were divided randomly into three groups and then were treated with anti-alpha 5 beta 1 integrin mAb-USPIO, naked USPIO and anti-alpha 5 beta 1 integrin mAb respectively. Abdominal magnetic resonance imaging (MRI) was performed for all rats before and 4 h after administration of the probes. The liver: muscle contrast-to-noise ratio (CNR) of the rats in all 4 groups before and 4 h after probe injection was calculated and analyzed. Liver tissue was subjected to pathologic scoring of fibrosis and location of iron particles of probes in normal and fibrosis rats was also observed. Results: The liver: muscle CNR 4 h after probes injection in hepatic fibrosis rats treated with anti-alpha 5 beta 1 integrin mAb-USPIO was much higher than that in normal rats treated with anti-alpha 5 beta 1 integrin mAb-USPIO and fibrosis rats treated with naked USPIO (P<0.01). Prussian blue staining and transmission electron microscopy demonstrated that the anti-alpha 5 beta 1 integrin mAb-USPIO probe was specifically engulfed by the activated HSCs in fibrosis rats. Conclusion: In vivo molecular MRI of activated HSCs in early stage of hepatic fibrosis rats was feasible by targeting alpha 5 beta 1 integrin with anti-alpha 5 beta 1 integrin mAb-USPIO probe.