Quantitative evaluation of hepatic integrin αvβ3 expression by positron emission tomography imaging using 18F-FPP-RGD2 in rats with non-alcoholic steatohepatitis

Background Integrin α v β 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 α v β 3 in a model of NASH by kinetic analysis using 18 F-FPP-RGD 2 , an integrin α v β 3 PET probe. Methods 18 F-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 α v or β 3 protein expression. Results Biochemical and histological evaluation confirmed the development of NASH rats. Integrin α v β 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. The V 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 α v and β 3 protein expression. The strengths of these correlations were similar to those between SUV 60–90 min and hepatic integrin α v or β 3 protein expression. Conclusions We have demonstrated that the V T (IDIF) of 18 F-FPP-RGD 2 , calculated using kinetic modelling, positively correlates with integrin α v and β 3 protein in the liver of NASH rats. These findings suggest that hepatic V T (IDIF) provides a quantitative assessment of integrin α v β 3 protein in liver.