STRUCTURAL AND DYNAMIC PARAMETERS OBTAINED FROM O-17 NMR, EPR, AND NMRD STUDIES OF MONOMERIC AND DIMERIC GD3-RESONANCE-IMAGING - AN INTEGRATED AND THEORETICALLY SELF-CONSISTENT APPROACH( COMPLEXES OF INTEREST IN MAGNETIC)

We present the results of new and previously published O-17 NMR, EPR, and NR?RD studies of aqueous solutions of the Gd3+ octaaqua ion and th e commercial MRI contrast agents [Gd(DTPA)(H2O)](2-) (MAGNEVIST, Scher ing AG, DTPA = 4,7,7-pentakis(carboxymethyl)-1,4,7-triazaheptane) [Gd( DTPA-BMA)(H2O)] (OMNISCAN, Sanofi Nycomed, DTPA-BMA = l]-1,4,7-tris(ca rboxymethyl)-1,4,7-triazaheptane), and [Gd(DOTA)(H2O)](-) (DOTAREM, Gu erbet, DOTA = is(carboxymethyl)-1,4,7,10-tetraazacyclododecane). High- field EPR measurements at different concentrations give evidence of an intermolecular dipole-dipole electronic relaxation mechanism that has not previously been described for Gd3+ complexes. For the first time, the experimental data from the three techniques for each complex have been treated using a self-consistent theoretical model in a simultane ous multiple parameter least-squares fitting procedure. The lower qual ity of the fits compared to separate fits of the data for each of the three techniques shows that the increase in the number of adjustable p arameters is outweighed by the increased constraint on the fits. The p arameters governing the relaxivity of the complexes are thus determine d with greater confidence than previously possible. The same approach was used to study two dimeric Gd3+ complexes [pip{Gd(DO3A)(H2O)}(2)] a nd [bisoxa{Gd(DO3A)(H2O)}(2)] (pip(DO3A)(2) = arboxymethyl)-1-cyclodod ecyl-1,4-diazacyclohexane, bisoxa-(DO3A)(2) = thyl)-1-cyclododecyl))-1 ,10-diaza-3,6-dioxadecane) that are being developed as potential secon d-generation MRT contrast agents. These dimeric complexes are expected to have higher relaxivities than the monomeric contrast agents, due t o their longer rotational correlation times. The results of this study show that further relaxivity gain for these complexes will be hindere d by the slow rate of water exchange on the complexes. High-field EPR measurements suggest that there is a previously unrecorded intramolecu lar dipole-dipole mechanism of electronic relaxation, but that this ad ditional contribution to electronic relaxation is of minor importance compared to the limiting effect of water exchange rates in the determi nation of proton relaxivity in MRI applications.