Evaluation of an Integrin αβ Radiotracer, [F]F-FPP-RGD, for Monitoring Pharmacological Effects of Integrin α siRNA in the NASH Liver.

Purpose: Integrin α is a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potential utility of an integrin αβ positron emission tomography (PET) radiotracer, F-labeled cyclic arginine-glycine-aspartic acid penta-peptide ([F]F-FPP-RGD), for detecting hepatic integrin α and function in nonalcoholic steatohepatitis (NASH) model rats using integrin α 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 protein, serum aspartate aminotransferase, and alanine aminotransferase were performed 1 week after single intravenous injection of integrin α siRNA.

Results: Integrin α siRNA (0.1 and 0.5 mg/kg) dose-dependently decreased hepatic integrin α protein concentrations in control and NASH model rats. The hepatic mean standard uptake value of [F]F-FPP-RGD was decreased dose-dependently by integrin α siRNA. The mean standard uptake value was positively correlated with integrin α 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 protein expression levels in NASH model rats.

Conclusion: This study suggests that [F]F-FPP-RGD PET imaging is a promising radiotracer for monitoring hepatic integrin α protein levels and hepatic function in NASH pathology.