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

DTPA-bisamide derivatives with alkyl chains containing 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 praseodymium(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, 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-gadolimurn complexes with C-14 and C-16 chains relative to the micellar DTPA-bisamide-Gd-III C-18 chain complex could be attributable to the fact that the alkyl chain containing 18 carbon atoms is longer than the alkyl chain of the major component of the micelles, DPPC, in which it is inserted. This would allow increased mobility of the polar head and hence a lower relaxivity. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.