Small-Animal SPECT/CT of the Progression and Recovery of Rat Liver Fibrosis by Using an Integrin αvβ3-targeting Radiotracer
Small-Animal SPECT/CT of the Progression and Recovery of Rat Liver Fibrosis by Using an Integrin αvβ3-targeting Radiotracer
复制标题
使用整合素αvβ3靶向放射性示踪剂进行小动物SPECT/CT观察大鼠肝纤维化的进展和恢复
DOI：
10.1148/radiol.2015150090
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发表时间：
2016-05-01
期刊：
影响因子：
19.7
通讯作者：
Wang, Fan
中科院分区：
文献类型：
--
作者：
Yu, Xinhe;Wu, Yue;Wang, Fan
目的：评价以整合素α(V)β(3)为靶向的放射性示踪剂~(2)Tc(99m-PEG(4)-E[PEG(4)-cyclo(arginineglycine-aspartic ACID-D-苯丙氨酸-赖氨酸)[2](~(99)m-3PRGD2)在单光子发射计算机体层摄影(SPECT)/计算机体层摄影术(CT)监测大鼠肝纤维化进展和预后中的作用。材料和方法：所有动物实验均按机构动物护理和使用委员会批准的方案进行。制备TC-99m-3PRGD2，用SPECT/CT纵向监测硫代乙酰胺(TAA)诱导的大鼠肝纤维化进展(n=8)和恢复(n=5)。在肝纤维化的不同阶段，TAA组和对照组(生理盐水)之间的平均肝本底放射性单位体积比被分析比较。数据采用t检验和Mann-Whitney检验进行比较。结果：TC-99m-3PRGD2在肝脏的蓄积量随肝纤维化的进展和TAA暴露时间的延长而增加，TAA组与对照组之间的蓄积水平早在TAA给药后第4周就有显著差异(肝本底比：32.30+/-3.39vs19.01+/-3.31；P=.0002)。体外免疫荧光染色结果显示，活化的肝星状细胞上整合素α(V)β(3)呈阳性表达，肝脏中整合素α(V)β(3)的水平与SPECT/CT结果一致(R2=0.75，P<；0.0001)。与对照组(相对肝本底比：0.45+/-0.05 vs 1.01+/-0.05；P<；0.0001)或自发恢复组(相对肝本底比：0.56+/-0.06 vs 1.01+/-0.05；P<；结论：TC-99m-3PRGD2 SPECT/CT可成功监测肝纤维化的进展和恢复，在早期肝纤维化的无创性诊断中具有潜在的应用价值。(C)RSNA，2015年
Purpose: To assess the potential utility of an integrin alpha(v)beta(3)-targeting radiotracer, technetium 99m-PEG(4)-E[PEG(4)-cyclo(arginineglycine-aspartic acid-D-phenylalanine-lysine)](2) (Tc-99m-3PRGD2), for single photon emission computed tomography (SPECT)/computed tomography (CT) for monitoring of the progression and prognosis of liver fibrosis in a rat model.Materials and Methods: All animal experiments were performed by following the protocol approved by the institutional animal care and use committee. Tc-99m-3PRGD2 was prepared and longitudinal SPECT/CT was performed to monitor the progression (n = 8) and recovery (n = 5) of liver fibrosis induced in a rat model by means of thioacetamide (TAA) administration. The mean liver-to-background radioactivity per unit volume ratio was analyzed for comparisons between the TAA and control (saline) groups at different stages of liver fibrosis. Data were compared by using Student t and Mann-Whitney tests. Results of SPECT/CT were compared with those of ex vivo biodistribution analysis (n = 5).Results: Accumulation of Tc-99m-3PRGD2 in the liver increased in proportion to the progression of fibrosis and TAA exposure time; accumulation levels were significantly different between the TAA and control groups as early as week 4 of TAA administration (liver-to-background ratio: 32.30 +/- 3.39 vs 19.01 +/- 3.31; P = .0002). Results of ex vivo immunofluorescence staining demonstrated the positive expression of integrin alpha(v)beta(3) on the activated hepatic stellate cells, and the integrin alpha(v)beta(3) levels in the liver corresponded to the results of SPECT/CT (R-2 = 0.75, P < .0001). Tc-99m-3PRGD2 uptake in the fibrotic liver decreased after antifibrotic therapy with interferon alpha(v)beta(3) compared with that in the control group (relative liver-to-background ratio: 0.45 +/- 0.05 vs 1.01 +/- 0.05; P < .0001) or spontaneous recovery (relative liver-to-background ratio: 0.56 +/- 0.06 vs 1.01 +/- 0.05; P < .0001).Conclusion: Tc-99m-3PRGD2 SPECT/CT was successfully used to monitor the progression and recovery of liver fibrosis and shows potential applications for noninvasive diagnosis of early stage liver fibrosis. (C) RSNA, 2015