Abstract
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.