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Journal of Biological Inorganic Chemistry

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Ligands (Biochemistry) -- Synthesis, Contrast media (Diagnostic imaging) -- Stability, Rare earth metals -- Magnetic properties, Magnetic resonance imaging


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.


This is the authors'version of a paper that subsequently appeared in the Journal of Biological Inorganic Chemistry, vol. 14, no. 3: 421–438.

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Note: At the time of writing Mark Woods was affiliated with the University of Texas at Dallas.



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