A magnetic resonance imaging modality for non-invasively distinguishing progression of liver fibrosis by visualizing hepatic platelet-derived growth factor receptor-beta expression in mice.

Background and aim Activated hepatic stellate cells (HSCs) are the most critical cells responsible for liver fibrosis, and platelet-derived growth factor (PDGF) is the most prominent mitogen for HSCs in fibrogenesis. This study aimed to explore the potential of gadolinium (Gd)-labelled cyclic peptides (pPB) targeting PDGF receptor-β (PDGFR-β) as a magnetic resonance imaging (MRI) radiotracer to identify the progression of liver fibrosis by imaging hepatic PDGFR-β expression. Methods Mice treated with carbon tetrachloride (CCl4 ) were used to mimic hepatic fibrosis in vivo. The binding activity of FITC-labelled pPB to PDGFR-β was assessed in cultured human HSCs (HSC-LX2). MRI was performed to visualize hepatic PDGFR-β expression in mice with different degrees of liver fibrosis after Gd-labelled pPB was injected. Results Hepatic PDGFR-β expression level was correlated with the severity of liver fibrosis, and the majority of cells expressing PDGFR-β were found to be activated HSCs in fibrotic livers. Culture-activated human HSCs expressed abundant PDGFR-β, and FITC-labelled pPB could bind to these cells in a concentration- and time-dependent manner. With Gd-labelled pPB as a tracer, an MRI modality demonstrated that the relative hepatic T1-weighted MRI signal value progressively increased with the severity of hepatic fibrosis, and reduced with remission. Conclusions Hepatic PDGFR-β expression reflects the progression of hepatic fibrosis, and MRI using Gd-labelled pPB as a tracer exhibits potential for distinguishing liver fibrosis staging in mice.