In vivo Overhauser-enhanced MRI of proteolytic activity
In vivo Overhauser-enhanced MRI of proteolytic activity
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DOI：
10.1002/cmmi.1586
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发表时间：
2014-09-01
影响因子：
--
通讯作者：
Mellet, Philippe
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文献类型：
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作者：
Koonjoo, Neha;Parzy, Elodie;Mellet, Philippe
有越来越多的兴趣在开发新的成像策略，在体内完整的生物体中的蛋白水解活性的传感。Overhauser增强MRI（OMRI）提供了一种可能性，以揭示蛋白水解的氮氧化物标记的大分子由于切割后的氮氧化物部分的旋转相关时间的急剧下降。在本文中，这一概念是说明在体内在0.2T使用一氧化氮标记的弹性蛋白口服给药小鼠。在体外，这种弹性蛋白衍生物是OMRI可见的，并且在胰腺猪弹性蛋白酶的蛋白水解后产生高的Overhauser增强（在18 mm氮氧化物下为19倍）。进行了蛋白水解的体内三维OMRI检测。使用锁孔完全平衡稳态自由旋进序列，允许在20 s内以0.125 mm（3）分辨率进行3D OMRI采集。小鼠灌胃后约30分钟，在十二指肠中检测到蛋白水解，其中Overhauser增强为7.2 +/- 2.4（n=7），在胃中未观察到。相反，口服给药的游离氮氧自由基或预消化的氮氧自由基标记的弹性蛋白检测小鼠的胃中的OMRI。结合特定的分子探针，这种Overhauser增强MRI技术可用于评估各种实验性疾病模型中不受调节的蛋白水解活性和药物测试。版权所有（c）2014约翰威利父子有限公司
There is an increasing interest in developing novel imaging strategies for sensing proteolytic activities in intact organisms in vivo. Overhauser-enhanced MRI (OMRI) offers the possibility to reveal the proteolysis of nitroxide-labeled macromolecules thanks to a sharp decrease of the rotational correlation time of the nitroxide moiety upon cleavage. In this paper, this concept is illustrated in vivo at 0.2T using nitroxide-labeled elastin orally administered in mice. In vitro, this elastin derivative was OMRI-visible and gave rise to high Overhauser enhancements (19-fold at 18mm nitroxide) upon proteolysis by pancreatic porcine elastase. In vivo three-dimensional OMRI detection of proteolysis was carried out. A keyhole fully balanced steady-state free precession sequence was used, which allowed 3D OMRI acquisition within 20s at 0.125mm(3) resolution. About 30min after mouse gavage, proteolysis was detected in the duodenum, where Overhauser enhancements were 7.2 +/- 2.4 (n=7) and was not observed in the stomach. Conversely, orally administered free nitroxides or pre-digested nitroxide-labeled elastin were detected in the mouse's stomach by OMRI. Combined with specific molecular probes, this Overhauser-enhanced MRI technique can be used to evaluate unregulated proteolytic activities in various models of experimental diseases and for drug testing. Copyright (c) 2014 John Wiley & Sons, Ltd.