Zhang Xin, Guo Qiyong, Shi Yu, Xu Weina, Yu Shupeng, Yang Zhiguang, Cao Li, Liu Changping, Zhao Zhoushe, Xin Jun
Department of Radiology and Nuclear Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Radiology and Nuclear Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
Nucl Med Biol. 2017 Jun;49:44-49. doi: 10.1016/j.nucmedbio.2017.02.004. Epub 2017 Mar 7.
Scintigraphy using 99mTc-3PRGD2 targeting integrin αvβ3 could assess activation of hepatic stellate cells (HSCs). Liver fibrogenesis is intimately associated with activation of HSCs, and the fibrolytic process is accompanied by the reduction of the activated HSCs. In this study, we aimed to evaluate the feasibility of this method to assess the severity of liver fibrosis and the reversal after the fibrotic stimulus withdrawal.
Liver fibrosis of different stages was induced by thioacetamide (TAA) injection for 2, 4 and 6 weeks (n = 6 for each time point). Another 6 rats with 8-week TAA administration (the 8-week group) and 6 rats which were injected with TAA for 6 weeks, and then withdrawn of TAA for 2 weeks (spontaneous recovery rats, SRR) were designed. The ratios of radioactivity detected in the liver vs. the heart at 30 min post-injection of Tc-3PRGD2 (L/H30), the collagen proportionate area (CPA), the protein and mRNA levels of integrin α, integrin β were analyzed and compared among groups.
The Ishak stage scores of the livers in the control and 2, 4, 6-week groups increased when the TAA administration period was extended. L/H30 increased with the upgrading of liver fibrosis and the differences between each pair of groups were statistically significant (p 30 min in the 8-week group was similar to that in the 6-week group (p > 0.05), but was significantly higher than that in the SRR group (p = 0.005).
Scintigraphy using Tc-3PRGD2 may provide a non-invasive method for grading liver fibrosis and assessing liver fibrosis reversal.
使用靶向整合素αvβ3的99mTc-3PRGD2进行闪烁扫描可评估肝星状细胞（HSC）的活化情况。肝纤维化与HSC的活化密切相关，而纤维溶解过程伴随着活化HSC数量的减少。在本研究中，我们旨在评估该方法评估肝纤维化严重程度以及纤维化刺激撤除后逆转情况的可行性。
通过注射硫代乙酰胺（TAA）2、4和6周诱导不同阶段的肝纤维化（每个时间点n = 6）。另外设计了6只接受8周TAA给药的大鼠（8周组）和6只注射TAA 6周然后撤除TAA 2周的大鼠（自发恢复大鼠，SRR）。分析并比较注射Tc-3PRGD2后30分钟肝脏与心脏放射性检测比值（L/H30）、胶原比例面积（CPA）、整合素α、整合素β的蛋白质和mRNA水平。
随着TAA给药时间延长，对照组以及2、4、6周组肝脏的Ishak分期评分升高。L/H30随着肝纤维化程度的升级而增加，各两两分组之间的差异具有统计学意义（p < 0.05）。8周组注射后30分钟的L/H30与6周组相似（p > 0.·05），但显著高于SRR组（p = 0.005）。
使用Tc-3PRGD2进行闪烁扫描可为肝纤维化分级和评估肝纤维化逆转提供一种非侵入性方法。
