Molecular imaging of oxidized collagen quantifies pulmonary and hepatic fibrogenesis
Molecular imaging of oxidized collagen quantifies pulmonary and hepatic fibrogenesis
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DOI：
10.1172/jci.insight.91506
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发表时间：
2017-06-02
期刊：
影响因子：
8
通讯作者：
Caravan, Peter
中科院分区：
文献类型：
--
作者：
Chen, Howard H.;Waghorn, Philip A.;Caravan, Peter
纤维化是由影响主要器官系统的组织修复机制失调引起的，导致慢性细胞外基质积聚和进行性的、通常致命的器官衰竭。目前的诊断依赖于侵入性活检。目前的非侵入性方法不能区分积极进行性纤维化与稳定性瘢痕，因此对监测疾病活动或治疗反应不敏感。胶原氧化是胶原交联之前活性纤维形成的普遍特征。生物化学靶向由赖氨酰氧化酶与小分子钆螯合物作用于胶原蛋白形成的氧化赖氨酸残基，能够实现靶向分子磁共振成像。这种对纤维化微环境的非侵入性直接生物化学阐明特异性和稳健地检测和分期肺和肝纤维化进展，并监测动物模型中的治疗反应。此外，这种范例是可转化的，并且通常适用于各种纤维增生性疾病。
Fibrosis results from the dysregulation of tissue repair mechanisms affecting major organ systems, leading to chronic extracellular matrix buildup, and progressive, often fatal, organ failure. Current diagnosis relies on invasive biopsies. Noninvasive methods today cannot distinguish actively progressive fibrogenesis from stable scar, and thus are insensitive for monitoring disease activity or therapeutic responses. Collagen oxidation is a universal signature of active fibrogenesis that precedes collagen crosslinking. Biochemically targeting oxidized lysine residues formed by the action of lysyl oxidase on collagen with a small-molecule gadolinium chelate enables targeted molecular magnetic resonance imaging. This noninvasive direct biochemical elucidation of the fibrotic microenvironment specifically and robustly detected and staged pulmonary and hepatic fibrosis progression, and monitored therapeutic response in animal models. Furthermore, this paradigm is translatable and generally applicable to diverse fibroproliferative disorders.