Synthesis and evaluation of lanthanide ion DOTA-tetraamide complexes bearing peripheral hydroxyl groups

Azhar Pasha, Mai Lin, Gyula Tircsó, Cynthia L. Rostollan, Mark Woods, Garry E. Kiefer, A. Dean Sherry, Xiankai Sun

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)421-438
Number of pages18
JournalJournal of Biological Inorganic Chemistry
Volume14
Issue number3
DOIs
StatePublished - Mar 2009

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Bearings (structural)
Lanthanoid Series Elements
Hydroxyl Radical
Contrast Media
Thermodynamics
Ions
Thermodynamic stability
Kinetics
Magnetic resonance
Magnetic Resonance Imaging
Toxicity
Acids
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
Imaging techniques
Serum

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

Cite this

Synthesis and evaluation of lanthanide ion DOTA-tetraamide complexes bearing peripheral hydroxyl groups. / Pasha, Azhar; Lin, Mai; Tircsó, Gyula; Rostollan, Cynthia L.; Woods, Mark; Kiefer, Garry E.; Sherry, A. Dean; Sun, Xiankai.

In: Journal of Biological Inorganic Chemistry, Vol. 14, No. 3, 03.2009, p. 421-438.

Research output: Contribution to journalArticle

Pasha, Azhar ; Lin, Mai ; Tircsó, Gyula ; Rostollan, Cynthia L. ; Woods, Mark ; Kiefer, Garry E. ; Sherry, A. Dean ; Sun, Xiankai. / Synthesis and evaluation of lanthanide ion DOTA-tetraamide complexes bearing peripheral hydroxyl groups. In: Journal of Biological Inorganic Chemistry. 2009 ; Vol. 14, No. 3. pp. 421-438.
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