Gadolinium-based contrast agents and their potential role in the pathogenesis of nephrogenic systemic fibrosis: The role of excess ligand
Gadolinium-based contrast agents and their potential role in the pathogenesis of nephrogenic systemic fibrosis: The role of excess ligand
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DOI：
10.1002/jmri.21368
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发表时间：
2008-05-01
影响因子：
4.4
通讯作者：
Pietsch, Hubertus
中科院分区：
文献类型：
--
作者：
Sieber, Martin A.;Lengsfeld, Philipp;Pietsch, Hubertus
目的：研究钆（Gd）造影剂中存在的过量配体在肾源性系统性纤维化（NSF）发生中的作用。使用给药方案，以模拟严重肾功能不全的患者中看到的暴露，我们研究了过量的配体对Gd沉积和内源性离子的消耗的影响。材料和方法：钆双胺和钆弗塞胺配制0%，5%和10%的过量配体。42只健康雄性汉诺威Wistar大鼠在20天内每日静脉注射每种制剂。在研究结束时，对皮肤进行组织病理学分析，并在几个组织中测量Gd、Zn和Cu的浓度。尿液中的锌的水平也measured.Results：最严重的皮肤病变后，观察到注射制剂含有0%的游离配体，并在这些动物的皮肤中的Gd浓度最高。在皮肤中观察到的Zn或Cu水平没有显著降低;然而，在施用具有最高量的过量配体的制剂后，尿液中的Zn水平升高。我们的研究结果表明，在含Gd造影剂中存在的过量配体的量与组织中Gd的量之间存在负相关，并进一步强调了这些试剂的内在稳定性在NSF开发中的重要性。
Purpose: To investigate the role of excess ligand present in gadolinium (Gd) -based contrast agents in the development of nephrogenic systemic fibrosis (NSF). Using a dosing regimen to simulate the exposure seen in patients with severe renal impairment, we investigated the effect of excess ligand on Gd-deposition and the depletion of endogenous ions.Materials and Methods: Gadodiamide and gadoversetamide were formulated with 0%, 5%, and 10% excess ligand. Forty-two, healthy, male Hannover Wistar rats received daily intravenous injections of each formulation over a period of 20 days. At the end of the study, histopathological analysis of the skin was performed and the concentrations of Gd, Zn, and Cu were measured in several tissues. The levels of Zn in the urine were also measured.Results: The most severe skin lesions were observed after injection of formulations containing 0% free ligand and in those animals with the highest Gd concentrations in the skin. There were no significant reductions in the levels of Zn or Cu observed in the skin; however, the levels of Zn in the urine were elevated following administration of formulations with the highest amount of excess ligand.Conclusion: Our findings suggest that there is an inverse correlation between the amount of excess ligand present in Gd-containing contrast agents and the amount of Gd in the tissue, and further underline the importance of the inherent stability of these agents in the development of NSF.