Cacheris W P, Quay S C, Rocklage S M
Salutar, Inc., Sunnyvale, CA 94086.
Magn Reson Imaging. 1990;8(4):467-81. doi: 10.1016/0730-725x(90)90055-7.
The suitability of gadolinium complexes as magnetic resonance imaging contrast agents depends on a number of factors. A thermodynamic relationship to toxicity exists if one assumes that the chemotoxicity of the intact complex is minimal but that the toxicity of the components of the complex (free metal and uncomplexed ligands) is substantial. Release of Gd3+ from the complex is responsible for the toxicity associated with gadolinium complexes; this release appears to be a consequence of Zn2+, Cu2+, and Ca2+ transmetallation in vivo. This hypothesis is supported by acute toxicity experiments, which demonstrate that despite a 50-fold range of LD50 values for four Gd complexes, all become lethally toxic when they release precisely the same quantity of Gd3+, and by subchronic rodent toxicity experiments, which demonstrate a set of gross and microscopic findings similar to those known to be caused by Zn2+ deficiency. Finally, this hypothesis predicts that subtle changes in formulation can further enhance the intrinsic safety of these complexes.
钆配合物作为磁共振成像造影剂的适用性取决于多个因素。如果假设完整配合物的化学毒性极小，但配合物组分（游离金属和未配位配体）的毒性很大，那么就存在与毒性相关的热力学关系。钆从配合物中的释放是导致钆配合物相关毒性的原因；这种释放似乎是体内锌离子、铜离子和钙离子发生金属转移作用的结果。急性毒性实验支持了这一假设，该实验表明，尽管四种钆配合物的半数致死剂量值相差50倍，但当它们释放出完全相同量的钆离子时，都会产生致命毒性；亚慢性啮齿动物毒性实验也支持了这一假设，该实验表明了一组与已知由锌缺乏引起的大体和微观表现相似的结果。最后，这一假设预测，配方中的细微变化可以进一步提高这些配合物的内在安全性。
