Evaluation of an Integrin αvβ3 Radiotracer, [18F]F-FPP-RGD2, for Monitoring Pharmacological Effects of Integrin αv siRNA in the NASH Liver

Purpose Integrin α v is a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potential utility of an integrin α v β 3 positron emission tomography (PET) radiotracer, 18 F-labeled cyclic arginine-glycine-aspartic acid penta-peptide ([ 18 F]F-FPP-RGD 2 ), for detecting hepatic integrin α v and function in nonalcoholic steatohepatitis (NASH) model rats using integrin α v siRNA. Methods NASH model rats were produced by feeding a choline-deficient, low-methionine, high-fat diet for 8 weeks. PET/computerized tomography imaging and quantification of integrin α v protein, serum aspartate aminotransferase, and alanine aminotransferase were performed 1 week after single intravenous injection of integrin α v siRNA. Results Integrin α v siRNA (0.1 and 0.5 mg/kg) dose-dependently decreased hepatic integrin α v protein concentrations in control and NASH model rats. The hepatic mean standard uptake value of [ 18 F]F-FPP-RGD 2 was decreased dose-dependently by integrin α v siRNA. The mean standard uptake value was positively correlated with integrin α v protein levels in control and NASH model rats. Serum aspartate aminotransferase and alanine aminotransferase concentrations were also decreased by siRNA injection and correlated with liver integrin α v protein expression levels in NASH model rats. Conclusion This study suggests that [ 18 F]F-FPP-RGD 2 PET imaging is a promising radiotracer for monitoring hepatic integrin α v protein levels and hepatic function in NASH pathology.