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Stability constants for Gd 3+ binding to model DTPA‐conjugates and DTPA‐proteins: Implications for their use as magnetic resonance contrast agents
Author(s) -
Sherry A. Dean,
Cacheris William P.,
Kuan KahTiong
Publication year - 1988
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.1910080208
Subject(s) - chemistry , macromolecule , conjugate , chelation , dota , amide , gadolinium , conjugated system , chemical stability , molecule , stability constants of complexes , nuclear magnetic resonance , polymer , inorganic chemistry , organic chemistry , biochemistry , mathematical analysis , physics , mathematics , aqueous solution
Five DTPA‐amide and ester derivatives have been synthesized and their Gd 3+ stability constants have been measured using a simple spectrophotometric method. These results are compared to stability constants measured for Gd 3+ binding to two different DTPA‐conjugated proteins. Although the thermodynamic constants for Gd 3+ binding to DTPA‐monopropylamide and DTPA‐monopropvlester relative to Gd( DTPA) 2− decrease by log K = 2.6 and 3.4, respectively, the blood pH conditional constants differ from Gd( DTPA) 2− only by log K = 1.2 and 1.9, respectively. The corresponding diprooylamide and ester conjugates of DTPA show considerably lower thermodynamic and conditional constants. This has important implications in the covalent attachment of chelates to macromolecules for use in magnetic resonance imaging. The measured binding constants for Gd(DTPA)‐IgG and Gd( DTPA)‐BSA suggest that many of the DTPA molecules in these systems, prepared under our experimental conditions, are diconjugated. The model compound results indicate that it is important to use methods in attaching DTPA to macromolecules which preclude diconjugation of the chelate. Otherwise, their affinity for Gd 3+ and consequently their usefulness as MRI contrast agents may be severely compromised. © 1988 Academic Press, Inc.