摘要
目的：通过对比肝损伤大鼠及正常大鼠肝脏在99mTc-3PRGD2靶向整合素αvβ3分子显像中的差异，评价该方法在诊断肝损伤中的应用价值。方法：应用硫代乙酰胺构建大鼠肝损伤模型（n=6），另外6只正常大鼠作为对照组。大鼠麻醉满意后，经尾静脉注射99mTc-3PRGD2，即刻行全身平面动态发射显像，于心脏及肝脏区域勾画大小为20像素的感兴趣区（ROI），计算显像第1、5、10、15、30、45、60、75、90 min肝脏与心脏ROI放射性计数比值（Liver-to-heart ratios，L/H），应用Mann-Whitney U检验比较各时间点两组间L/H的差异，应用受试者工作特征曲线（ROC曲线）评价两组间L/H有统计学差异时间点在预测肝损伤的能力，选择约登指数最大者作为截断点，得到相应的敏感度与特异度。大鼠显像后处死，取肝组织进行HE染色、天狼猩红胶原染色及整合素αvβ3免疫组化染色。结果：肝损伤组各显像时间点L/H均高于正常对照组，但两组L/H仅在显像第30 min有统计学差异（P＜0.05），此时ROC曲线下面积（AUC）为0.917，截断点为1.58（约登指数0.883，敏感度100%，特异度88.3%）。HE染色及天狼猩红染色可见损伤组大鼠肝脏内大量的肝细胞呈气球样变，但无确切胶原纤维的沉积（Ishak分级评分=0或1）。肝损伤组大鼠肝脏内整合素αvβ3弥漫性表达，而对照组大鼠肝脏内无表达。结论：99mTc-3PRGD2靶向整合素αvβ3分子显像可通过监测整合素αvβ3表达的升高，作为诊断肝损伤及早期肝纤维化的灵敏的、无创性手段，显像适宜时间点在99mTc-3PRGD2注射后30 min。
Abstract
Objective: To evaluate the application of molecular imaging using 99mTc-3PRGD2 targeting integrin αvβ3 for diagnosis of liver injury by comparing the imaging difference between the rats with liver injury and the control ones. Methods: Six thioacetamide-induced liver injury rat models and 6 control rats were used. All the rats after satisfied anesthesia were performed whole-body planar dynamic scintigraphy immediately after the injection of 99mTc-3PRGD2 through the tail vein. The region of interest(ROI) with an area of 20 pixels was positioned in the region of liver and heart for each rat, and the liver-to-heart ratios(L/H) at 1, 5, 10, 15, 30, 45, 60, 75 and 90 min were calculated. The difference of L/H at each time point between the two groups was compared by Mann-Whitney U test, and receiver operating characteristic curve(ROC curve) was used to calculate the cutoff value with the biggest Youden’s index and the corresponding sensitivity and specificity. The liver tissue was harvested after execution and performed HE and Sirius red staining, as well as immunohistochemistry of integrin αvβ3. Results: L/H of the liver-injured group at all the time points were bigger than those of the control group, however only the difference between the two groups at 30 min post-injection of 99mTc-3PRGD2 was statistically significant(P＜0.05). The area under the curve(AUC) was 0.917, and the cutoff value was 1.58 with the Youden’s index 0.883, the sensitivity 100% and the specificity 88.3%. A large amount of ballooning degeneration liver cells in the liver-injured group was observed on the HE and Sirius red staining liver sections without apparent deposition of fibrosis(Ishak stage score=0 or 1). The diffusely positive expression of integrin αvβ3 was observed in the liver-injured group, and no positive expression was observed in the control group. Conclusion: Molecular imaging using 99mTc-3PRGD2 targeting integrin αvβ3 may be a sensitive and non-invasive method for the diagnosis of liver injury and early-stage liver fibrosis by evaluating the increased expression of integrin αvβ3, and the optimal time point for imaging is 30 min post-injection.
关键词
肝疾病 /
放射性核素显像
Key words
Liver diseases /
Radionuclide imaging
张 新;辛 军;赵周社;曹 礼;石 喻;郭启勇.
99mTc-3PRGD2靶向整合素αvβ3分子显像在评价肝损伤的初步研究[J]. 中国临床医学影像杂志. 2014, 25(6): 401-405
ZHANG Xin;XIN Jun;ZHAO Zhou-she;CAO Li;SHI Yu;GUO Qi-yong.
The initial study of 99mTc-3PRGD2 molecular imaging targeting integrin αvβ3 in evaluation of liver injury[J]. Journal of China Clinic Medical Imaging. 2014, 25(6): 401-405
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