Nucl Med Mol Imaging.  2023 Aug;57(4):172-179. 10.1007/s13139-023-00791-9.

Evaluation of an Integrin α_vβ₃ Radiotracer, ­[¹⁸F]F‑FPP‑RGD₂ , for Monitoring Pharmacological Effects of Integrin α_v siRNA in the NASH Liver

• Hiroyama S
• Matsunaga K
• Ito M
• Iimori H
• Morita I
• Nakamura J
• Shimosegawa E
• Abe K

• KMID: 2545313
• DOI: http://doi.org/10.1007/s13139-023-00791-9

Abstract

Purpose
Integrin αv is a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potential utility of an integrin α_vβ₃ positron emission tomography (PET) radiotracer, ¹⁸F-labeled cyclic arginine-glycine-aspartic acid penta-peptide ([¹⁸F]F-FPP-RGD2), for detecting hepatic integrin αv and function in nonalcoholic steatohepatitis (NASH) model rats using integrin αv 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 αv 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 [¹⁸F]F-FPP-RGD₂ was decreased dose-dependently by integrin αv 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 αv protein expression levels in NASH model rats.
Conclusion
This study suggests that [¹⁸F]F-FPP-RGD₂ PET imaging is a promising radiotracer for monitoring hepatic integrin α_v protein levels and hepatic function in NASH pathology.

Keyword

Nonalcoholic steatohepatitis (NASH); Arginine-glycine-aspartic (RGD); Positron emission tomography (PET); Small interfering RNA (siRNA); Integrin