2ND-SPHERE AND OUTER-SPHERE PROTON RELAXATION OF PARAMAGNETIC-COMPLEXES - FROM EPR TO NMRD

Magnetic resonance imaging often utilizes paramagnetic contrast agents (PCAs) to increase contrast between adjacent tissues. PCAs enhance th e contrast by increasing the spin-lattice proton relaxation rate throu gh processes known as inner-sphere, second-sphere, and outer-sphere me chanisms. Past studies on PCAs often described relaxation rates that a re not caused by inner-sphere processes as outer-sphere, since compara tively little is known about second-sphere water. Utilizing vanadyl co mplexes (ethylenediaminetetraacetate (EDTA) and diethylenetriaminepent aacetate (DTPA)) that do not have an inner-sphere proton relaxation co ntribution and those with similar functional groups of different sizes , we find that the outer-sphere model does not adequately describe the relaxivity profiles. The observed relaxivity profiles are, however, c onsistent with a model that includes both second-sphere and outer-sphe re contributions. Vanadyl ethoxybenzyl-diethylenetriaminepentaacetate (VOEOB-DTPA) exhibited relaxivity similar to that of DTPA, even though it is larger. This is attributed to a hydrophobic moiety on EOB-DTPA that prevents protons from binding to the second coordination sphere. The combined model developed for the vanadyl complexes is used to simu late the gadolinium triethylenetetraaminehexaacetate (GdTTHA) proton N MRD profile, and the results are extrapolated to deconvolute GdDTPA an d GdEOB-DTPA proton NMRD profiles into inner-sphere, second-sphere, an d outer-sphere contributions. We find that the second-sphere mechanism is significant and may contribute about 30% of the relaxivity in GdDT PA and about 10% in GdEOB-DTPA.