Evaluation of an Integrin αvβ3 Radiotracer, [18F]F-FPP-RGD2, for Monitoring Pharmacological Effects of Integrin αv siRNA in the NASH Liver

Shuichi Hiroyama; Keiko Matsunaga; Miwa Ito; Hitoshi Iimori; Ippei Morita; Jun Nakamura; Eku Shimosegawa; Kohji Abe

doi: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

Nucl Med Mol Imaging. 2023 Aug;57(4):172-179. doi: 10.1007/s13139-023-00791-9. Epub 2023 Mar 7.

Authors

Shuichi Hiroyama¹, Keiko Matsunaga², Miwa Ito¹, Hitoshi Iimori³, Ippei Morita³, Jun Nakamura³, Eku Shimosegawa², Kohji Abe¹

Affiliations

¹ Biomarker R&D Department, Shionogi & Co., Ltd., 3-1-1 Futaba-Cho, Toyonaka, Osaka 561-0825 Japan.
² Department of Molecular Imaging in Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
³ Laboratory for Advanced Medicine Research, Shionogi & Co., Ltd., Osaka, Japan.

PMID: 37483876
PMCID: PMC10359219 (available on 2024-08-01)
DOI: 10.1007/s13139-023-00791-9

Abstract

Purpose: Integrin α_v 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 α_v and function in nonalcoholic steatohepatitis (NASH) model rats using integrin α_v 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_v 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 α_v 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 α_v 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.

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

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