Imaging of myeloperoxidase in mice by using novel amplifiable paramagnetic substrates
Imaging of myeloperoxidase in mice by using novel amplifiable paramagnetic substrates
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DOI：
10.1148/radiol.2402050994
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发表时间：
2006-08-01
期刊：
影响因子：
19.7
通讯作者：
Weissleder, Ralph
中科院分区：
文献类型：
--
作者：
Chen, John W.;Sans, Manel Querol;Weissleder, Ralph
目的：评估用于分子磁共振（MR）成像的造影剂是否能够显示髓过氧化物酶在体内的活性，髓过氧化物酶是一种在炎症过程中由受刺激的多形核白细胞、单核细胞和巨噬细胞分泌的酶。
材料与方法：动物实验经动物护理委员会批准。获取和使用人血的方案经机构审查委员会批准。从每位捐赠者处获得知情同意，并且对人类遵循《健康保险流通与责任法案》（HIPAA）指南。合成了两种顺磁性髓过氧化物酶底物，即钆 - 5 - 羟基色胺 - 四氮杂环十二烷四乙酸（Gd - 5 - HT - DOTA）和钆 - 双 - 5 - HT - 二乙三胺五乙酸（Gd - 双 - 5 - HT - DTPA）。铟111标记的双 - 5 - HT - DTPA用于确定生物分布和靶向定位。在三个模型中总共使用了22只小鼠。在第一个模型中，人髓过氧化物酶被包埋在基底膜基质凝胶中并肌肉注射。在第二个模型中，大肠杆菌的脂多糖（LPS）被包埋在基底膜基质凝胶中并肌肉注射以诱导内源性髓过氧化物酶分泌。在第三个模型中，LPS肌肉注射以诱导肌炎。通过使用柯尔莫哥洛夫 - 斯米尔诺夫检验计算对比噪声比（CNR）曲线的统计学意义。
结果：给予Gd - 双 - 5 - HT - DTPA后，磁共振信号显著增强（CNR增加高达2.5倍，P <...（此处原文似乎不完整）
Purpose: To evaluate whether contrast agents for molecular magnetic resonance (MR) imaging can demonstrate the in vivo activity of myeloperoxidase, an enzyme that is secreted by stimulated polymorphonuclear leukocytes, monocytes, and macrophages during inflammation.Materials and Methods: Animal experiments were approved by the animal care committee. Protocols for the procurement and use of human blood were approved by the institutional review board. Informed consent was obtained from each donor, and HIPAA guidelines were followed for humans. Two paramagnetic myeloperoxidase substrates-that is, gadolinium-5-hydroxytryptamide-tetraazacyclododecane tetraacetic acid (Gd-5-HT-DOTA) and Gd-bis-5-HT-diethylenetriaminepentaacetic acid (Gd-bis-5-HT-DTPA)-were synthesized. Indium 111-labeled bis-5-HT-DTPA was used to determine biodistribution and target localization. A total of 22 mice were used in three models. In the first model, human myeloperoxidase was embedded in a basement membrane matrix gel and was injected intramuscularly. In the second model, lipopolysaccharide (LPS) from Escherichia coli was embedded in a basement membrane matrix gel and was injected intramuscularly to induce endogenous myeloperoxidase secretion. In the third model, LPS was injected intramuscularly to induce myositis. Statistical significance was calculated for contrast-to-noise ratio (CNR) curves by using the Kolmogorov-Smirnov test.Results: After the administration of Gd-bis-5-HT-DTPA, strong MR signal enhancement (up to 2.5-fold increase in CNR, P