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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

        Shuichi Hiroyama,Keiko Matsunaga,Miwa Ito,Hitoshi Iimori,Ippei Morita,Jun Nakamura,Eku Shimosegawa,Kohji Abe 대한핵의학회 2023 핵의학 분자영상 Vol.57 No.4

        Purpose Integrin αv is a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potentialutility of an integrin αvβ3 positron emission tomography (PET) radiotracer, 18F-labeled cyclic arginine-glycine-aspartic acidpenta-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 alanineaminotransferase 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 incontrol and NASH model rats. The hepatic mean standard uptake value of [18F]F-FPP-RGD2 was decreased dose-dependentlyby integrin αv siRNA. The mean standard uptake value was positively correlated with integrin αv protein levels in controland NASH model rats. Serum aspartate aminotransferase and alanine aminotransferase concentrations were also decreasedby 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 integrinαv protein levels and hepatic function in NASH pathology.

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