Non-Invasively Distinguishing Progress of Liver Fibrosis by Visualizing Hepatic Platelet Derived Growth Factor Receptor-Beta Expression with an MRI Modality in Mice

Background: Activated hepatic stellate cells are the most critical cell responsible for liver fibrosis. In liver fibrogenesis, platelet-derived growth factor is the most prominent mitogen for hepatic stellate cells. This study aims to explore the potential of gadolinium (Gd)-labeled cyclic peptides (pPB) targeted to platelet-derived growth factor receptor-β (PDGFR-β) as a magnetic resonance imaging (MRI) radiotracer to identify the progress of liver fibrosis by imaging hepatic PDGFR-β expression. Results: Hepatic PDGFR-β expression level was found to be paralleled with the severity of liver fibrosis, which was increased with the progression of fibrosis and reduced with the regression. Majority of cells expressing PDGFR-β was determined to be activated hepatic stellate cells in fibrotic livers. Culture-activated human hepatic stellate cells expressed abundant PDGFR-β, and FITC-labeled pPB could bind to human hepatic stellate cells in a concentration and time dependent manner. With Gd-labeled pPB as a tracer, an MRI modality demonstrated that the relative hepatic T1-weighed MR signal value was increased progressively along with severity of hepatic fibrosis and reduced with the remission. Conclusion: Hepatic PDGFR-β expression reflects the progress of hepatic fibrosis, and MR imaging using Gd-labeled pPB as a tracer may distinguish different stages of liver fibrosis in mice.