H-1 and O-17-NMR relaxometric investigations of paramagnetic contrast agents for MRI. Clues for higher relaxivities

The analysis of H-1- and O-17-NMR relaxometric data allows us to get a bett er insight into the understanding of the structural and dynamic factors res ponsible for the relaxivity of a given paramagnetic system. High relaxiviti es are obtained in the presence crf a long molecular reorientational time a nd fast exchange of the water molecule(s) coordinated to the paramagnetic m etal ion. Long molecular reorientational times are pursued either through t he formation of covalent conjugates between a paramagnetic complex and a ma cromolecular substrate or through the formation of non-covalent adducts bet ween suitably functionalized complexes and endogenous (e.g. serum albumin) or exogenous (e.g. poly-beta-cyclodextrin) substrates. Within the class of covalent conjugates, it has been shown that the use of a DOTA-like chelate bearing the squaric acid as linking moiety leads to an improved relaxivity with respect to analogous systems obtained through reactions involving the bifunctional DTPA bisanhydride. As far as the exchange of the coordinated w ater in Gd(III) chelates is concerned, it depends on the energy difference between the ground ennea-coordinated state and the activated octa-coordinat ed state. in the presence of bulky substituents, the ground state is destab ilized with a consequent increase of the exchange rate. An elongation of th e exchange lifetime can occur upon the interaction with serum albumin. This behaviour may result in a decrease of the attainable relaxivity. Finally, it has been shown that Mn(II) chelates may represent a viable alternative t o Gd(III) complexes. In fact,in spite of the lower effective magnetic momen t, the non-covalent adducts between Mn(II) chelates and albumin display ver y high relaxivities. This result has been accounted for in terms of the ver y short exchange lifetime of the Mn(II) coordinated water molecule. (C) 199 9 Elsevier Science S.A. All rights reserved.