Pasha Azhar, Lin Mai, Tircsó Gyula, Rostollan Cynthia L, Woods Mark, Kiefer Garry E, Sherry A Dean, Sun Xiankai
Department of Chemistry, University of Texas at Dallas, P.O. Box 803066, Richardson, TX 75083, USA.
J Biol Inorg Chem. 2009 Mar;14(3):421-38. doi: 10.1007/s00775-008-0459-3. Epub 2008 Dec 13.
The use of lanthanide-based contrast agents for magnetic resonance imaging has become an integral component of this important diagnostic modality. These inert chelates typically possess high thermodynamic stability constants that serve as a predictor for in vivo stability and low toxicity. Recently, a new class of contrast agents was reported having a significantly lower degree of thermodynamic stability while exhibiting biodistribution profiles indicative of high stability under biological conditions. These observations are suggestive that the nature of contrast agent stability is also dependent upon the kinetics of complex dissociation, a feature of potential importance when contemplating the design of new chelates for in vivo use. We present a study of the kinetics of acid-catalyzed dissociation, thermodynamic stability, serum stability, and biodistribution of a series of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-tetraamide complexes that have been substituted with peripheral hydroxyl groups. The data indicate that these nontraditional contrast agents exhibit in vivo stability comparable to that of agents with much higher log K (ML) values, demonstrating the important contribution of kinetic inertness.
基于镧系元素的造影剂在磁共振成像中的应用已成为这一重要诊断方式不可或缺的组成部分。这些惰性螯合物通常具有较高的热力学稳定性常数，可作为体内稳定性和低毒性的预测指标。最近，有报道称一类新型造影剂的热力学稳定性显著降低，同时在生物条件下呈现出高稳定性的生物分布特征。这些观察结果表明，造影剂稳定性的本质还取决于络合物解离的动力学，这一特性在考虑设计用于体内的新型螯合物时可能具有重要意义。我们对一系列用外周羟基取代的1, 4, 7, 10-四氮杂环十二烷-1, 4, 7, 10-四乙酸（DOTA）-四酰胺配合物的酸催化解离动力学、热力学稳定性、血清稳定性和生物分布进行了研究。数据表明，这些非传统造影剂在体内的稳定性与log K(ML)值高得多的造影剂相当，证明了动力学惰性的重要贡献。
