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

• Published in: Nuclear medicine and molecular imaging Vol. 57; no. 4; p. 172
• Main Authors: Hiroyama, Shuichi, Matsunaga, Keiko, Ito, Miwa, Iimori, Hitoshi, Morita, Ippei, Nakamura, Jun, Shimosegawa, Eku, Abe, Kohji
• Format: Journal Article
• Language: English
• Published: Germany 01.08.2023
• Subjects: Positron emission tomography (PET); Integrin; Arginine-glycine-aspartic (RGD); Small interfering RNA (siRNA); Nonalcoholic steatohepatitis (NASH)
• ISSN: 1869-3474

Integrin α is a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potential utility of an integrin α β 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. 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. 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. 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.