[钆螯合物作为磁共振成像造影剂的物理化学和毒理学特性]

[Physico-chemical and toxicological profile of gadolinium chelates as contrast agents for magnetic resonance imaging].

作者信息

Idée J-M, Fretellier N, Thurnher M M, Bonnemain B, Corot C

机构信息

Guerbet, division recherche et innovation, BP 57400, 95943 Roissy-Charles De Gaulle cedex, France.

Guerbet, division recherche et innovation, BP 57400, 95943 Roissy-Charles De Gaulle cedex, France.

出版信息

Ann Pharm Fr. 2015 Jul;73(4):266-76. doi: 10.1016/j.pharma.2015.01.001. Epub 2015 Feb 27.

Abstract

Gadolinium chelates (GC) are contrast agents widely used to facilitate or to enable diagnosis using magnetic resonance imaging (MRI). From a regulatory viewpoint, GC are drugs. GC have largely contributed to the success of MRI, which has become a major component of clinician's diagnostic armamentarium. GC are not metabolised and are excreted by the kidneys. They distribute into the extracellular compartment. Because of its high intrinsic toxicity, gadolinium must be administered as a chelate. GC can be classified according to two key molecular features: (a) nature of the chelating moiety: either macrocyclic molecules in which gadolinium is caged in the pre-organized cavity of the ligand, or linear, open-chain molecules, (b) ionicity: Gd chelates can be ionic (meglumine or sodium salts) or non-ionic. The thermodynamic and kinetic stabilities of the various GCs differ according to these structural characteristics. The kinetic stability of macrocyclic GCs is much higher than that of linear GCs and the thermodynamic stability of ionic GCs is generally higher than that of non-ionic GC, thus leading to a lower risk of gadolinium dissociation. This class of drugs has enjoyed an excellent reputation in terms of safety for a long time, until a causal link with a recently-described serious disease, nephrogenic systemic fibrosis (NSF), was evidenced. It is acknowledged that the vast majority of NSF cases are related to the administration of some linear CG in renally-impaired patients. Health authorities, worldwide, released recommendations which drastically reduced the occurrence of new cases.

摘要

钆螯合物(GC)是广泛用于促进或实现磁共振成像(MRI)诊断的造影剂。从监管角度来看,GC属于药物。GC在很大程度上促成了MRI的成功,MRI已成为临床医生诊断手段的主要组成部分。GC不会被代谢,而是通过肾脏排泄。它们分布于细胞外间隙。由于钆具有高内在毒性,必须以螯合物形式给药。GC可根据两个关键分子特征进行分类:(a)螯合部分的性质:要么是钆被封闭在配体预先形成的腔内的大环分子,要么是线性开链分子;(b)离子性:钆螯合物可以是离子型(葡甲胺盐或钠盐)或非离子型。各种GC的热力学和动力学稳定性根据这些结构特征而有所不同。大环GC的动力学稳定性远高于线性GC,离子型GC的热力学稳定性通常高于非离子型GC,因此导致钆解离的风险较低。这类药物长期以来在安全性方面享有良好声誉,直到有证据表明与一种最近描述的严重疾病——肾源性系统性纤维化(NSF)存在因果关系。人们认识到,绝大多数NSF病例与在肾功能受损患者中使用某些线性CG有关。世界各地的卫生当局发布了相关建议,大幅减少了新病例的发生。

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