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Molecular imaging of hepatic stellate cell activity by visualization of hepatic integrin αvβ3 expression with SPECT in rat
Author(s) -
Li Feng,
Song Zhengji,
Li Qinghua,
Wu Jian,
Wang Jiyao,
Xie Cao,
Tu Chuantao,
Wang Jian,
Huang Xiaowei,
Lu Weiyue
Publication year - 2011
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24467
Subject(s) - hepatic stellate cell , integrin , hepatic fibrosis , fibrosis , biology , thioacetamide , pathology , receptor , chemistry , endocrinology , medicine , biochemistry
The key factors in the pathogenesis of liver fibrosis are the activation and proliferation of hepatic stellate cells (HSCs), which express integrin αvβ3 after activation. This study aimed to explore the potential of 99m Tc‐labeled cyclic arginine‐glycine‐aspartic acid pentapeptide (cRGD) as a single photon emission computed tomography (SPECT) radiotracer to image hepatic integrin αvβ3 expression to reflect HSC activity in fibrotic livers. Rat models of liver fibrosis caused by thioacetamide or carbon tetrachloride (CCl 4 ) treatment were employed to examine the expression and distribution of integrin αvβ3 during fibrotic progression or regression. The binding activity of radiolabeled cRGD to integrin αvβ3 was assessed in liver sections. SPECT was performed to determine hepatic integrin αvβ3 expression in rats with different stages of liver fibrosis. Protein and messenger RNA (mRNA) levels of integrin αv and β3 subunits were increased with the progression of liver fibrosis and reduced with its regression. The cell type that expressed the majority of integrin αvβ3 in fibrotic livers was found to be activated HSCs. The cRGD binding to activated HSCs displayed a high receptor‐coupling affinity and an abundant receptor capacity. Iodine‐125 ( 125 I)‐labeled cRGD bound to fibrotic liver sections and the binding activity was the highest in advanced fibrosis. Intravenously administered carboxyfluorescein‐labeled cRGD was accumulated in fibrotic liver, and the accumulation amount was increased with the progression and reduced with the regression of fibrosis. A SPECT imaging study with 99m Tc‐labeled cRGD as a tracer demonstrated that the radioactivity ratio of liver to heart increased progressively along with severity of hepatic fibrosis. Conclusion: Hepatic integrin αvβ3 expression in fibrotic liver reflects HSC activity and its imaging using 99m Tc‐labeled cRGD as a SPECT radiotracer may distinguish different stages of liver fibrosis in rats. (H EPATOLOGY 2011;)