Preparation, physico-chemical characterization, and relaxometry studies of various gadolinium(III)-DTPA-bis(amide) derivatives as potential magnetic resonance contrast agents

C. F G C Geraldes, A. M. Urbano, M. C. Alpoim, A. D. Sherry, K. T. Kuan, R. Rajagopalan, F. Maton, R. N. Muller

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Macroscopic protonation constants were measured for a series of DTPA mono- and bis-amide ligands using potentiometric titrations. Proton NMR pH titrations yielded protonation populations of the various nitrogen and oxygen basic sites of the ligands for the different protonation stages. Amide formation decreased the basicity of the backbone nitrogens of the ligands and the thermodynamic stability of the corresponding Gd3+ chelates. Nuclear magnetic relaxation dispersion (NMRD) profiles and ESR linewidths were measured for the Gd3+ chelates. Some of these exhibited an elevated high field relaxivity relative to Gd(DTPA)2-, in response to their high molecular weight. As opposed to Gd(DTPA)2-, at 5°C the chemical exchange process of the single inner-sphere water molecule of the bis-amide complexes becomes so slow that it governs the paramagnetic relaxation process, causing the observed NMRD profiles to be close to those expected for the outer-sphere contribution. The chelates containing long alkyl side chains, such as Gd(DTPA-HPA2), showed increased relaxivity values in the presence of human serum albumin (HSA), indicative of noncovalent interaction with the protein. These chelates could be useful as nonionic hepatobiliary contrast agents.

Original languageEnglish (US)
Pages (from-to)401-420
Number of pages20
JournalMagnetic Resonance Imaging
Volume13
Issue number3
DOIs
StatePublished - 1995

Fingerprint

Pentetic Acid
Gadolinium DTPA
Gadolinium
Magnetic resonance
gadolinium
Amides
chelates
Contrast Media
amides
magnetic resonance
Protonation
Magnetic Resonance Spectroscopy
Magnetic relaxation
Derivatives
preparation
Ligands
magnetic relaxation
Titration
titration
ligands

Keywords

  • Electron spin resonance (ESR)
  • Gd(DTPA)
  • Gd chelates
  • Nuclear magnetic relaxation dispersion (NMRI)

ASJC Scopus subject areas

  • Biophysics
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Clinical Biochemistry
  • Structural Biology
  • Condensed Matter Physics

Cite this

Preparation, physico-chemical characterization, and relaxometry studies of various gadolinium(III)-DTPA-bis(amide) derivatives as potential magnetic resonance contrast agents. / Geraldes, C. F G C; Urbano, A. M.; Alpoim, M. C.; Sherry, A. D.; Kuan, K. T.; Rajagopalan, R.; Maton, F.; Muller, R. N.

In: Magnetic Resonance Imaging, Vol. 13, No. 3, 1995, p. 401-420.

Research output: Contribution to journalArticle

Geraldes, C. F G C ; Urbano, A. M. ; Alpoim, M. C. ; Sherry, A. D. ; Kuan, K. T. ; Rajagopalan, R. ; Maton, F. ; Muller, R. N. / Preparation, physico-chemical characterization, and relaxometry studies of various gadolinium(III)-DTPA-bis(amide) derivatives as potential magnetic resonance contrast agents. In: Magnetic Resonance Imaging. 1995 ; Vol. 13, No. 3. pp. 401-420.
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