Chen John W, Pham Wellington, Weissleder Ralph, Bogdanov Alexei
Center for Molecular Imagina Research, Massachusetts General Hospital, Charlestown 02129, USA.
Magn Reson Med. 2004 Nov;52(5):1021-8. doi: 10.1002/mrm.20270.
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.
动脉粥样硬化疾病中的斑块破裂是发病的主要原因，并且与人类活化的中性粒细胞和巨噬细胞分泌髓过氧化物酶（MPO）密切相关。我们推测，可以设计出在MPO存在下能快速氧化并聚合的顺磁性电子供体化合物，以实现对有风险动脉段局部MPO活性水平的成像。合成并测试了几种MPO的潜在底物。一种由钆喷酸葡胺（GdDOTA）与血清素（3-(2-氨基乙基)-5-羟基吲哚）的共价共轭物组成的先导化合物，在人中性粒细胞MPO存在下能有效聚合，导致质子弛豫率提高70%-100%。因此，我们能够在酶溶液和类组织模型系统中证明MPO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成像MPO活性。
