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2006-01-01 - Article/Dans un journal avec peer-review - Anglais - 12 page(s)

Parac-Vogt T.N., Vander Elst Luce , Kimpe K., Laurent Sophie , Burtea Carmen , Chen F., Vand Deun R., Ni Y.C., Muller Robert , Binnemans K., "Pharmacokinetic and in vivo evaluation of a self-assembled gadolinium(III)-iron(II) contrast agent with high relaxivity" in Contrast Media & Molecular Imaging, 1, 6, 267-278

  • Edition : John Wiley & Sons, Inc, Chichester (United Kingdom)
  • Codes CREF : Résonance magnétique nucléaire (biophysique) (DI131B), Chimie de coordination (DI1319), Pharmacocinétique (DI3431), Chimie organique (DI1313), Imagerie médicale, radiologie, tomographie (DI3243)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108)
Texte intégral :

Abstract(s) :

(Anglais) A high-molecular weight tetrametallic supramolecular complex [(Ln-DTPA-phen)(3)Fe](-) (Ln=Gd, Eu, La) has been obtained upon self-assembly around one iron(II) ion of three 1,10-phenantroline-based molecules substituted in 5'-position with the polyaminocarboxylate diethylenetriamine-N,N,N',N",N"-pentaacetate, DTPA-phen(4-). The ICP-MS measurements indicated that the lanthanide:iron ratio is 3:1. Photoluminescence spectra of [Eu-DTPA-phen](-) and of [(Eu-DTPA-phen)(3)Fe](-) are nearly identical, implying that the first coordination sphere of the lanthanide(III) ion has not been changed upon coordination of phenantroline unit to iron(II) ion. NMRD measurements revealed that at 20 MHz and 310 K the relaxivity of the [(Gd-DTPA-phen)(3)Fe](-) is equal to 9.5 +/- 0.3 s(-1) mM(-1) of Gd (28.5 s(-1) per millimole per liter of complex) which is significantly higher than that for Gd-DTPA (3.9 s(-1) mM(-1)). The pharmacokinetic parameters of [(Gd-DTPA-phen)(3)Fe](-) in rats indicate that the elimination of [(Gd-DTPA-phen)(3)Fe](-) is significantly slower than that of Gd-DTPA and is correlated with a reduced volume of distribution. The low volume of distribution and the longer elimination time (T-e1/2) suggest that the agent is confined to the blood compartment, so it could have an important potential as a blood pool contrast agent. The biodistribution profile of [(Gd-DTPA-phen)(3)Fe](-) 2 h after injection indicates significantly higher concentrations of [(Gd-DTPA-phen)(3)Fe](-) as compared with Gd-DTPA in kidney, liver, lungs, heart and spleen. The images obtained on rats by MR angiography show the enhancement of the abdominal blood vessels. The signal intensity reaches a maximum of 55% at 7 min post-contrast and remains around 25% after 90 min. MRI-histomorphological correlation studies of [Gd-DTPA-phen]- and [(Gd-DTPA-phen)(3)Fe](-) showed that both agents displayed potent contrast enhancement in organs including the liver. The necrosis avidity tests indicated that, in contrast to the [Gd-DTPA-phen]- precursor complex, the supramolecular complex [(Gd-DTPA-phen)(3)Fe](-) exhibits necrosis avidity.

Identifiants :
  • PMID : 17191767
  • DOI : 10.1002/cmmi.114

Mots-clés :
  • (Anglais) MRI contrast agents
  • (Anglais) pharmacokinetics
  • (Anglais) magnetic resonance imaging