Human myeloperoxidase: A potential target for molecular MR imaging in atherosclerosis
Human myeloperoxidase: A potential target for molecular MR imaging in atherosclerosis
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DOI：
10.1002/mrm.20270
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发表时间：
2004-11-01
影响因子：
3.3
通讯作者：
Bogdanov, A
中科院分区：
文献类型：
--
作者：
Chen, JW;Pham, W;Bogdanov, A
动脉粥样硬化疾病中的斑块破裂是发病的主要原因，并且与人类体内活化的中性粒细胞和巨噬细胞分泌的髓过氧化物酶（MPO）密切相关。我们假设，在MPO存在的情况下能迅速氧化和聚合的顺磁性电子供体化合物可被设计用于对有风险的动脉段局部MPO活性水平进行成像。几种潜在的MPO底物被合成并进行了测试。一种由钆-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（GdDOTA）和血清素（3 -（2 - 氨基乙基）- 5 - 羟基吲哚）共价结合组成的先导化合物在人中性粒细胞MPO存在的情况下能有效地聚合，导致质子弛豫率提高70 - 100%。因此，我们能够在酶溶液和类似组织的模型系统中证明MPO的活性。这些研究表明，可激活的顺磁性磁共振成像剂可用于直接对MPO活性进行成像。（C）2004威利 - 利斯公司
Plaque rupture in atherosclerotic disease is the major cause of morbidity and correlates well with myeloperoxidase (MPO) secretion by activated neutrophils and macrophages in humans. We hypothesized that paramagnetic electron donor compounds that rapidly oxidize and polymerize in the presence of MPO could be designed to enable imaging of local MPO activity levels in arterial segments at risk. Several potential substrates for MPO were synthesized and tested. One lead compound consisting of a covalent conjugate of GdDOTA and serotonin (3-(2-aminoethyl)-5-hydroxyindole) was efficiently polymerized in the presence of human neutrophil MPO resulting in a 70-100% increase in proton relaxivity. As a result, we were able to demonstrate MPO activity in enzyme solutions and in a model tissue-like system. These studies suggest that activatable paramagnetic MR imaging agents can be used to directly image MPO activity. (C) 2004 Wiley-Liss, Inc.