Potential MRI contrast agents based on micellar incorporation of amphiphilic bis(alkylamide) derivatives of [(Gd-DTPA)(H2O)]2-

MRI (magnetic resonance imaging) contrast agents are routinely used in medicine because they are able to produce reliable results that help in rapid clinical interpretation of images and simultaneously improve the patient turnover. Most of the commonly used contrast agents achieve their effect by enhancing the relaxation rate of water protons in tissues. In general contrast agents consist of a paramagnetic metal centre, typically Gd3+, which is complexed with a strong chelating ligand, since the free metal ions are toxic at the concentrations needed for diagnosis[1-2]. In recent years complexes of lanthanides with diethylenetriamine-N,N,N,’N,”N”-pentaacetate (DTPA5-) and with its amide derivatives have attracted considerable attention. The anionic [Gd(DTPA)(H2O)]2-, the first contrast agent approved for use in humans, is nowadays routinely used in clinical magnetic resonance imaging for contrast enhancement under the name Magnevist® (Schering, Berlin, Germany). This paramagnetic complex contains one inner-sphere water molecule [3-6] that exchanges rapidly [7] with the bulk water in the human body, therefore providing an efficient mechanism for the enhancement of the relaxation rates of the water protons. In attempt to achieve higher proton relaxivity, DTPA-bisamide derivatives with alkyl chains consisting of 14, 16, and 18 carbon atoms were synthesized and complexes of various trivalent lanthanide ions (Ln = Gd, La, Pr, Eu) were formed. Variable temperature proton NMR spectroscopy of paramagnetic praseodynium(III) and europium(III) complexes revealed that long aliphatic substituents considerably increase the energy barrier for the intramolecular rearrangement around the lanthanide ion. The gadolinium(III) complexes were incorporated into mixed micelles (DPPC and Tween 80®) and photon correlation spectroscopy showed that the mean sizes of all the micelles were within the same range. The NMRD-curves of all three DTPA-bisamide-gadolinium complexes incorporated in mixed micelles display higher relaxivity values than the commercially available Gd-DTPA contrast agent. The higher relaxivity obtained for the micellar DTPA-bisamide-gadolinium complexes with C14 and C16 chains as compared to the micellar DTPA-bisamide-Gd(III) complex with C18 chain could be attributed to the fact that the alkyl chain consisting of 18 carbon atoms is longer than the alkyl chain of the major component of the micelles, DPPC, in which it is inserted. This allows an increased mobility of the polar head and hence a lower relaxivity. References: 1. Rinck, PA. Magnetic Resonance in Medicine; Blackwell Scietific Publications; Oxford, UK, 1993. 2. S. Aime, M. Botta, M. Fasano, E. Terreno “Lanthanide(III) chelates fot NMR biomedical applications” Chemical Society Reviews 27 (1998) 19-29. 3. C. C. Bryden, C. N. Reilley, Anal.Chem. 1982, 54, 610-615. 4. J. A. Peters, Inorg. Chem. 1988, 27, 4686-4691. 5. C. F. G. C. Geraldes, A. D. Sherry, W. P. Cacheris, K. T. Kuan, R.D. Brown III, S. H. Koenig, M. Spiller, Magn. Reson. Med. 1988, 8, 191-199. 6. C. A. Chang, H. G. Brittain, J. Telser, M. F. Tweedle, Inorg. Chem. 1990, 29, 4468-4473. 7. K. Micskei, L. Helm, E. Brucher, A. E. Merbach, Inorg. Chem. 1993, 32, 3844-3850. 56poster presented by Kristof Kimpestatus: publishe

Low-field NMR water proton longitudinal relaxation in ultrahighly diluted aqueous solutions of silica-lactose prepared in glass material for pharmaceutical use

Low-field (0.02-4 MHz) proton nuclear magnetic resonance (NMR) longitudinal relaxometry was applied to ultrahighly diluted aqueous solutions in order to detect physical modifications induced in the solvent by the dilution process. A mixture of silica-lactose (1.67·10-5 M silica, 2.92·10-2 M lactose) was initially solubilized in water or in saline, then submitted to eighteen iterative centesimal dilutions in water or in saline under vigorous vortex agitation and rigorously controlled atmospheric conditions, and compared to similarly treated pure water and saline as controls. Several independent series of samples were measured according to a blind protocol (total of 140 code-labelled samples). A slight frequency dispersion (about 4%) was found within the 0.02-4 MHz range, centered around 0.55 MHz, and ascribed to combined effects of silica and trace paramagnetic contaminants, both concentrated and in a reduced motion at the borosilicate wall tube interface. The iterative dilution-agitation process in pure water and saline induced no significant effect on relaxivity. Slightly increased relaxivity compared to solvent was found in the initial silica-lactose dilution (especially in saline, about 4%), which vanished unexpectedly slowly upon dilution, as adjusted to an arbitrary log-linear model. Statistical analysis was applied to succeed in discriminating solutions from their solvents beyond the 10-12 level of dilution. No clear explanation emerged, but post-experiment chemical analysis revealed high amounts (6 ppm) of released silica from the glass material used, with excess in silica-lactose samples, and lower amounts of trace paramagnetic contaminants in highly diluted silica-lactose samples, which could provide a clue.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Kêpoi

Ce volume de mélanges sur le thème des Jardins reflète les préoccupations scientifiques d’André Motte à qui il fut offert : le vocabulaire grec du sacré, les jardins, les prairies et tous les lieux poétiques et religieux de la métaphore végétale, quelques dieux grecs liés à ces manifestations, quelques-unes des étapes essentielles de la philosophie antique, Platon, Aristote, Lucrèce, avec leurs éventuels prolongements contemporains, mais aussi les penseurs du christianisme naissant et l’histoire des religions pratiquée par Franz Cumont