Among the lanthanide ions, gadolinium is known as the best nuclear relaxation enhancer of longitudinal nuclear relaxation because of its long electronic relaxation time. Its stable complexes are thus widely used as T 1 contrast agents for MRI. Complexes of other paramagnetic lanthanides (III) are usually utilized as shift agents in NMR spectroscopy or as susceptibility agents in MRI. For example, Dy-complexes have been proposed to measure cerebral blood volume (1) and to delineate healthy and damaged tissues (2-7) by MRI. After injection, Dy-complexes are localized in the extracellular compartment of healthy tissues, and as a result of their relatively large magnetic susceptibility, they induce local field gradients that result in a T* 2 decrease. However, this type of T * 2 effect requires quite large concentrations of the compound. In damaged areas where cell membranes are disrupted, Dy-complexes are homogeneously distributed and have very little influence on the T* 2 at the magnetic fields used in MRI.For lanthanide ions characterized by very short electronic relaxation times, such as Dy(III), Pr(III), Sm(III), Ho(III), Er(III), and Yb(III), a sizable contribution to longitudinal nuclear proton relaxation resulting from the presence of a large static magnetic moment at high magnetic fields has been proposed by Bertini et al. (8). This contribution, first described by Guéron (9) and called Curie relaxation, originates from the dipolar interaction between the water protons and a large static magnetic moment arising from the electrons. In 1991, Aime et al. (10) suggested taking advantage of the dependence of the proton transverse relaxation rate vs. the square of the magnetic field to reduce the water proton signal in high-field NMR spectra. These authors also showed that the efficacy of the water suppression depends on the structure of the complex, and they attributed this to different exchange rates of the coordinated water with the bulk. More recently, because of the above-mentioned high-field effect on the water protons, Dy(III) complexes were suggested as potential negative contrast agents for MRI (11,12).In the present work, we report experimental evidence of the Curie longitudinal relaxation of different Dy-complexes of similar size, and illustrate the influence of the magnetic field and the residence time of the coordinated water molecule on the proton transverse relaxation rate. Five open-chain Dy(III) complexes were studied: 1) the parent compound Dy(DTPA) 2Ϫ (DTPA: 3,6,9-tris(carboxymethyl)-3,6,9-triazaundecanedioic acid); and four bisamide derivatives: 2) Dy(DTPA-BA) (DTPA-BA: 3,9-bis(2-amino-2-oxoethyl)-6-(carboxymethyl)-3,6,9-triazaundecanedioic acid); 3) Dy(DTPA-BEA) (DTPA-BEA: 3,9-bis(2-ethylamino-2-oxoethyl)-6-(carboxymethyl)-3,6,9-triazaundecanedioic acid); 4) Dy(DTPA-BnBA) (DTPA-BnBA: 3,9-bis(2-n-butylamino-2-oxoethyl)-6-(carboxymethyl)-3,6,9-triazaundecanedioic acid); and 5) Dy(DTPA-BBMA) (DTPA-BBMA: 3,9-bis(2,2-bismethylamino-2-oxoethyl)-6-(carboxymethyl)-3,6,9-triazaundecanedioic acid) (Fig...

Such a synergistic effect of noncovalent PEGylation of poly(amino methacrylate)/DNA complexes allows a new and versatile approach to tune up transfection efficiency.

In our efforts of finding new specific contrast agents of higher relaxivity and selectivity, we have prepared the two new benzyl-functionalized DTPA (−diethylenetriamine pentaacetate×) gadolinium complexes (S)-3 and (R,S)-4, and compared their properties with those of the known regioisomers (S)-2 and (S)-1. The theoretical fitting of the reduced transverse relaxation rates of the 17 O-nucleus of H 2 O gave values for the water-residence time (t M ) of 86 ± 143 ns at 310 K, values that are not limiting the proton relaxivity at body temperature. 1 H-NMRD (nuclear magnetic-relaxation dispersion) Profiles showed that the relaxivity of 1 ± 4 (r 1 4.3 ± 5.1 s À1 mm À1 at 20 MHz and 310 K) is higher than for the GdÀDTPA parent compound 5. Transmetallation assessment demonstrated that all substituted compounds, except for (S)-2, are more stable than 5. The highest stability towards Zn 2 -induced transmetallation was achieved with complexes 3, 1, and 4 (in decreasing order). Apparently, the steric hindrance of the benzyl substituents in positions 5, 4, and 2, respectively, favorably reduces the accessibility of Zn ions. From a synthetic point of view, 4-substituted DTPA complexes of type 1 are more readily accessible than 5-substituted compounds of type 3. Therefore, the former seem to be superior for linking substituted DTPA complexes to macromolecules or specific vectors.

No abstract

No abstract