Quantitative evaluation of hepatic integrin αβ expression by positron emission tomography imaging using F-FPP-RGD in rats with non-alcoholic steatohepatitis.

Background: Integrin αβ, which are expressed by activated hepatic stellate cells in non-alcoholic steatohepatitis (NASH), play an important role in the fibrosis. Recently, we reported that an RGD peptide positron emission tomography (PET) probe is useful as a predictor of hepatic fibrosis. Kinetic analysis of the RGD PET probe has been performed in tumours, but not in hepatic fibrosis. Therefore, we aimed to quantify hepatic integrin αβ in a model of NASH by kinetic analysis using F-FPP-RGD, an integrin αβ PET probe.

Methods: F-FPP-RGD PET/CT scans were performed in control and NASH rats. Tissue kinetic analyses were performed using a one-tissue, two-compartment (1T2C) and a two-tissue, three-compartment (2T3C) model using an image-derived input function (IDIF) for the left ventricle. We then conducted correlation analysis between standard uptake values (SUVs) or volume of distribution (V), evaluated using compartment kinetic analysis and integrin α or β protein expression.

Results: Biochemical and histological evaluation confirmed the development of NASH rats. Integrin αβ protein expression and hepatic SUV were higher in NASH- than normal rats. The hepatic activity of F-FPP-RGD peaked rapidly after administration and then gradually decreased, whereas left ventricular activity rapidly disappeared. The 2T3C model was found to be preferable for F-FPP-RGD kinetic analysis in the liver. The V for F-FPP-RGD, calculated using the 2T3C model, was significantly higher in NASH- than normal rats and correlated strongly with hepatic integrin α and β protein expression. The strengths of these correlations were similar to those between SUV and hepatic integrin α or β protein expression.

Conclusions: We have demonstrated that the V of F-FPP-RGD, calculated using kinetic modelling, positively correlates with integrin α and β protein in the liver of NASH rats. These findings suggest that hepatic V provides a quantitative assessment of integrin αβ protein in liver.