DI-UMONS : Dépôt institutionnel de l’université de Mons

Recherche transversale
(titres de publication, de périodique et noms de colloque inclus)
2006-11-17 - Colloque/Présentation - communication orale - Anglais - 1 page(s)

Henoumont Céline , Laurent Sophie , Henrotte Virginie, Vander Elst Luce , Muller Robert , "Investigation of non covalent interactions between some MRI contrast agents and HSA by proton relaxometry and NMR diffusometry" in 5th one-day symposium Young Belgian Magnetic Resonance Scientists, Bruxelles, Belgique, 2006

  • Codes CREF : Résonance magnétique nucléaire (biophysique) (DI131B)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)

Abstract(s) :

(Anglais) Nowadays, magnetic resonance imaging (MRI) is more and more used in the medical field. As compared to other imaging techniques, its spatial and temporal resolutions are better but its sensibility is relatively weak. In most cases, the use of contrast agents is required. Most of them are gadolinium complexes, which have the property of increasing the signal of the pathological zones, improving the image contrast. Very efficient contrast agents, i.e. contrast agents with a high proton relaxivity, are thus needed. This can be obtained for example with molecules interacting non-covalently with endogenous macromolecules, like human serum albumin (HSA). It is thus very important to have at one’s disposal some techniques allowing the evaluation of this type of non-covalent interactions. In this work, two NMR techniques are studied and compared to evaluate the interaction of six MRI contrast agents with HSA : - Proton relaxometry1,2 : the water longitudinal relaxation rate is measured in the presence of HSA 4% and of various contrast agent concentrations. This method gives rapid information on the affinity for HSA but the estimation of the association constant can be ambiguous since several parameters of the theoretical model are strongly correlated. - NMR diffusometry3 : the variation of the ligand diffusion coefficient in the absence and in the presence of HSA is studied. However, this high resolution NMR technique does not allow to use gadolinium complexes because of the signal broadening they produce. Europium complexes were thus used since this lanthanide has the advantage of shifting the ligand signals outside of the HSA background without inducing significant broadening of the peaks. The results show that this technique does not allow to distinguish weak and high affinity ligand binding. In fact, if the ligand interacts too strongly with HSA, the exchange between free and bound states is too slow and no significant evolution of the diffusion coefficient can be detected, as it would be the case for a ligand which has no affinity for HSA. Competition experiments with competitors of known binding site on HSA (ibuprofen and salicylic acid), have been performed with both techniques and compared. These experiments were very helpful and allowed to specify the binding site of the contrast agents on HSA and the strength of their interaction with the protein. 1. Vander Elst, L., Maton, F., Laurent, S., Seghi, F., Chapelle, F., Muller, R.N., Magn. Res. Med. 1997, 38, 604-614 2. Muller, R.N., Radüchel, B., Laurent, S., Platzek, J., Piérart, C., Mareski, P., Vander Elst, L., Eur. J. Inorg. Chem. 1999, 1949-1955 3. Lucas, L.H., Larive, C.K., Conc. Magn. Res. 2004, Part A, 20A(1), 24-41