Development of magnetic resonance imaging contrast material for in vivo mapping of tissue transglutaminase activity
Development of magnetic resonance imaging contrast material for in vivo mapping of tissue transglutaminase activity
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DOI：
10.1158/0008-5472.can-04-2269
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发表时间：
2005-02-15
期刊：
影响因子：
11.2
通讯作者：
Neeman, M
中科院分区：
文献类型：
--
作者：
Mazooz, G;Mehlman, T;Neeman, M
谷氨酰胺转胺酶是一类酶，通过催化细胞外基质蛋白之间的共价交联在组织重塑中发挥重要作用。谷氨酰胺转氨酶活性升高显示在侵袭肿瘤的边界，与血管生成，动脉粥样硬化斑块的稳定和血凝块的产生有关。这项工作的目的是开发一种低分子量的谷氨酰胺酶底物，可以用于无创磁共振和光学定位谷氨酰胺酶介导的交联活性。生成2 kDa的造影剂，分别在多细胞肿瘤球体或纤维蛋白凝块的情况下由组织转谷氨酰胺酶或因子XIII交联。通过核磁共振显微镜成功检测到转谷氨酰胺酶介导的造影剂与MCF7多细胞球体的交联，为这种方法可能用于临床划分转谷氨酰胺酶活性位点提供了希望。
Transglutaminases are a family of enzymes that play an important role in tissue remodeling by catalyzing covalent cross-links between proteins of the extracellular matrix. Elevated activity of transglutaminase was shown at the boundaries of invading tumors, in association with angiogenesis, in stabilization of atherosclerotic plaques, and in generation of blood clots. The aim of this work was to develop a low molecular weight substrate of transglutaminase that could serve for noninvasive magnetic resonance and optical mapping of transglutaminase-mediated cross-linking activity. A 2 kDa contrast material was generated which showed cross-linking by either tissue transglutaminase or factor XIII in the context of multicellular tumor spheroids or fibrin clots, respectively. Successful detection by nuclear magnetic resonance microscopy of transglutaminase-mediated cross-linking of the contrast material to MCF7 multicellular spheroids provides hope that this approach could potentially be developed for clinical demarcation of sites of transglutaminase activity.