Quantitative evaluation of hepatic integrin alpha(v)beta(3)expression by positron emission tomography imaging using(18)F-FPP-RGD(2)in rats with non-alcoholic steatohepatitis

Background Integrin alpha(v)beta(3), 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 alpha(v)beta(3)in a model of NASH by kinetic analysis using(18)F-FPP-RGD(2), an integrin alpha(v)beta 3PET probe. Methods F-18-FPP-RGD(2)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-T), evaluated using compartment kinetic analysis and integrin alpha(v)or beta(3)protein expression. Results Biochemical and histological evaluation confirmed the development of NASH rats. Integrin alpha(v)beta(3)protein expression and hepatic SUV were higher in NASH- than normal rats. The hepatic activity of(18)F-FPP-RGD(2)peaked rapidly after administration and then gradually decreased, whereas left ventricular activity rapidly disappeared. The 2T3C model was found to be preferable for(18)F-FPP-RGD(2)kinetic analysis in the liver. TheV(T (IDIF))for(18)F-FPP-RGD(2), calculated using the 2T3C model, was significantly higher in NASH- than normal rats and correlated strongly with hepatic integrin alpha(v)and beta(3)protein expression. The strengths of these correlations were similar to those between SUV(60-90 min)and hepatic integrin alpha(v)or beta(3)protein expression. Conclusions We have demonstrated that theV(T (IDIF))of(18)F-FPP-RGD(2), calculated using kinetic modelling, positively correlates with integrin alpha(v)and beta(3)protein in the liver of NASH rats. These findings suggest that hepaticV(T (IDIF))provides a quantitative assessment of integrin alpha(v)beta(3)protein in liver.