In vivo imaging of inflammation using an aptamer inhibitor of human neutrophil elastase

In vivo imaging of inflammation using an aptamer inhibitor of human neutrophil elastase
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DOI:
10.1016/s1074-5521(97)90114-9
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发表时间:
1997-11-01
影响因子:
--
通讯作者:
Smith, D
Smith, D
中科院分区:
生物1区
文献类型:
--
作者:
Charlton, J;Sennello, J;Smith, D

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背景:我们先前报道了人中性粒细胞弹性蛋白酶不可逆抑制剂适体的分离。我们现在报告的应用适体技术的诊断imaging.Results领域:弹性蛋白酶已被报道结合到活化的中性粒细胞的表面。使用荧光流式细胞术测定,我们表明,弹性蛋白酶的适体抑制剂也优先结合到活化的中性粒细胞。然后,我们在大鼠反向被动Arthus反应模型中测试了适体在体内成像炎症的能力。适体在2小时内达到4.3 +/-0.6的峰值靶-背景(T/B)比。临床上用于炎症成像的IgG需要更长的时间才能在3小时达到较低的T/B:3.1 +/- 0.1。T/B值的差异是由于。结论:将适体配体应用于诊断成像是可行的,其中它们可以提供比单克隆抗体和其他试剂显著的优势。
Background: We previously reported the isolation of aptamer irreversible inhibitors of human neutrophil elastase. We now report on the application of aptamer technology to the field of diagnostic imaging.Results: The enzyme elastase has been reported to bind to the surface of activated neutrophils. Using a fluorescent flow cytometry assay, we showed that an aptamer inhibitor of elastase also binds preferentially to activated neutrophils. We then tested the ability of the aptamer to image inflammation in vivo in a rat reverse passive Arthus reaction model. The aptamer achieved a peak target-to-background (T/B) ratio of 4.3 +/- 0.6 in 2 hours. IgG, which is used clinically to image inflammation, took a longer time to achieve a lower T/B: 3.1 +/- 0.1 at 3 hours. The difference in T/B values is due. to the faster clearance of the aptamer signal from the blood pool.Conclusions: It is feasible to apply aptamer ligands for use in diagnostic imaging, where they may offer significant advantages over monoclonal antibodies and other reagents.