Evaluation of an Integrin alpha(v)beta(3) Radiotracer, [F-18]F-FPP-RGD(2), for Monitoring Pharmacological Effects of Integrin alpha(v) siRNA in the NASH Liver

PurposeIntegrin alpha(v) is a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potential utility of an integrin alpha(v)beta(3) positron emission tomography (PET) radiotracer, F-18-labeled cyclic arginine-glycine-aspartic acid penta-peptide ([F-18]F-FPP-RGD(2)), for detecting hepatic integrin alpha(v) and function in nonalcoholic steatohepatitis (NASH) model rats using integrin alpha(v) siRNA.MethodsNASH 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 alpha(v) protein, serum aspartate aminotransferase, and alanine aminotransferase were performed 1 week after single intravenous injection of integrin alpha(v) siRNA.ResultsIntegrin alpha(v) siRNA (0.1 and 0.5 mg/kg) dose-dependently decreased hepatic integrin alpha(v) protein concentrations in control and NASH model rats. The hepatic mean standard uptake value of [F-18]F-FPP-RGD(2) was decreased dose-dependently by integrin alpha(v) siRNA. The mean standard uptake value was positively correlated with integrin alpha(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 alpha(v) protein expression levels in NASH model rats.ConclusionThis study suggests that [F-18]F-FPP-RGD(2) PET imaging is a promising radiotracer for monitoring hepatic integrin alpha(v) protein levels and hepatic function in NASH pathology.