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KMID : 1148920230570040172
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Nuclear Medicine and Molecular Imaging
2023 Volume.57 No. 4 p.172 ~ p.179
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Evaluation of an Integrin αvβ3 Radiotracer, [18F]F-FPP-RGD2, for Monitoring Pharmacological Effects of Integrin αv siRNA in the NASH Liver
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Shuichi Hiroyama
Keiko Matsunaga
Miwa Ito
Hitoshi Iimori
Ippei Morita
Jun Nakamura
Eku Shimosegawa
Kohji Abe
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Abstract
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Purpose : Integrin αv is a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potential utility of an integrin αvβ3 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 αv siRNA.
Results : Integrin αv siRNA (0.1 and 0.5 mg/kg) dose-dependently decreased hepatic integrin αv 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 αv 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 αv protein levels and hepatic function in NASH pathology.
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KEYWORD
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Nonalcoholic steatohepatitis (NASH), Arginine-glycine-aspartic (RGD), Positron emission tomography (PET), Small interfering RNA (siRNA), Integrin
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