TY - JOUR
T1 - Synthesis and evaluation of lanthanide ion DOTA-tetraamide complexes bearing peripheral hydroxyl groups
AU - Pasha, Azhar
AU - Lin, Mai
AU - Tircsó, Gyula
AU - Rostollan, Cynthia L.
AU - Woods, Mark
AU - Kiefer, Garry E.
AU - Sherry, A. Dean
AU - Sun, Xiankai
N1 - Funding Information:
Acknowledgments The authors thank the National Institutes of Health (RR-02584, CA-126608, CA119219, and CA-115531) and the Robert A Welch Foundation (AT-584) for financial assistance. X.S. also acknowledges the support of his start-up funds provided by the Harold C. Simmons Comprehensive Cancer Center and the Department of Radiology of University of Texas Southwestern Medical Center at Dallas.
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
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U2 - 10.1007/s00775-008-0459-3
DO - 10.1007/s00775-008-0459-3
M3 - Article
C2 - 19083028
AN - SCOPUS:61849163928
SN - 0949-8257
VL - 14
SP - 421
EP - 438
JO - Journal of Biological Inorganic Chemistry
JF - Journal of Biological Inorganic Chemistry
IS - 3
ER -