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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Molecular Imaging of Hepatic Stellate Cell Activity by Visualization of Hepatic Integrin alphavbeta3 Expression with SPECT in Rat
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Molecular Imaging of Hepatic Stellate Cell Activity by Visualization of Hepatic Integrin alphavbeta3 Expression with SPECT in Rat

机译：用SPECT观察大鼠肝脏整联蛋白αvbeta3表达的肝脏星状细胞活性的分子成像。

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The key factors in the pathogenesis of liver fibrosis are the activation and proliferation of hepatic stellate cells (HSCs), which express integrin alphavbeta3 after activation. This study aimed to explore the potential of ~(99m)Tc-labeled cyclic arginine-glycine-aspartic acid penta-peptide (cRGD) as a single photon emission computed tomography (SPECT) radiotracer to image hepatic integrin alphavbeta3 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 alphavbeta3 during fibrotic progression or regression. The binding activity of radiolabeled cRGD to integrin alphavbeta3 was assessed in liver sections. SPECT was performed to determine hepatic integrin alphavbeta3 expression in rats with different stages of liver fibrosis. Protein and messenger RNA (mRNA) levels of integrin alphav and beta3 subunits were increased with the progression of liver fibrosis and reduced with its regression. The cell type that expressed the majority of integrin alphavbeta3 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 alphavbeta3 expression in fibrotic liver reflects HSC activity and its imaging using ~(99m)Tc-labeled cRGD as a SPECT radiotracer may distinguish different...
机译：肝纤维化发病机制中的关键因素是肝星状细胞（HSC）的激活和增殖，该星状细胞在激活后表达整合素alphavbeta3。这项研究旨在探讨〜（99m）Tc标记的环状精氨酸-甘氨酸-天冬氨酸五肽（cRGD）作为单光子发射计算机断层摄影（SPECT）放射性示踪剂的潜能，以成像肝脏整联蛋白alphavbeta3表达以反映HSC活性。肝纤维化。采用硫代乙酰胺或四氯化碳（CCl_4）处理引起的大鼠肝纤维化模型，检查在纤维化进展或消退过程中整联蛋白alphavbeta3的表达和分布。在肝脏切片中评估了放射性标记的cRGD与整联蛋白alphavbeta3的结合活性。进行了SPECT，以确定具有不同肝纤维化阶段的大鼠中肝整联蛋白αvbeta3的表达。整联蛋白αv和β3亚基的蛋白质和信使RNA（mRNA）水平随着肝纤维化的进展而增加，而随着其消退而降低。发现在纤维化肝脏中表达大多数整合素αvbeta3的细胞类型是活化的HSC。 cRGD与激活的HSC的结合表现出高的受体偶联亲和力和丰富的受体能力。碘125（〜（125）I）标记的cRGD与肝纤维化切片结合，在晚期纤维化中结合活性最高。静脉注射羧基荧光素标记的cRGD积累在纤维化肝脏中，并且积累量随着进展而增加，随着纤维化的消退而减少。以〜（99m）Tc标记的cRGD作为示踪剂的SPECT成像研究表明，肝与心脏的放射性比随着肝纤维化的严重程度而逐渐增加。结论：纤维化肝中肝脏整合素alphavbeta3的表达反映了HSC活性，并且使用〜（99m）Tc标记的cRGD作为SPECT放射性示踪剂对其成像可以区分不同的...

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