Evaluation of an Integrin αvβ3Radiotracer, [18F]F-FPP-RGD2, for Monitoring Pharmacological Effects of Integrin αvsiRNA in the NASH Liver

Purpose: Integrin α_vis a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potential utility of an integrin α_vβ₃positron emission tomography (PET) radiotracer, ¹⁸F-labeled cyclic arginine-glycine-aspartic acid penta-peptide ([¹⁸F]F-FPP-RGD₂), for detecting hepatic integrin α_vand function in nonalcoholic steatohepatitis (NASH) model rats using integrin α_vsiRNA. 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_vprotein, serum aspartate aminotransferase, and alanine aminotransferase were performed 1 week after single intravenous injection of integrin α_vsiRNA. Results: Integrin α_vsiRNA (0.1 and 0.5 mg/kg) dose-dependently decreased hepatic integrin α_vprotein concentrations in control and NASH model rats. The hepatic mean standard uptake value of [¹⁸F]F-FPP-RGD₂was decreased dose-dependently by integrin α_vsiRNA. The mean standard uptake value was positively correlated with integrin α_vprotein 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_vprotein expression levels in NASH model rats. Conclusion: This study suggests that [¹⁸F]F-FPP-RGD₂PET imaging is a promising radiotracer for monitoring hepatic integrin α_vprotein levels and hepatic function in NASH pathology.