Gd(DTPA-bisamide)alkyl copolymers: A hint for the formation of MRI contrast agents with very high relaxivity

A variable-temperature, multiple-field O-17 NMR and EPR spectroscopic study has been performed on three Gd(DTPA-bisamide)alkyl copolymers, [Gd(DTPA-BA )-(CH2)(n)](x) (n = 6, 10, 12; DTPA = diethylenetriamine-N,N,N',N ",N'''-pe ntaacetate). The rate and mechanism of water exchange is identical for the polymer complexes and [Gd(DTPA-BMA)(H2O)], which can be considered as the m onomer unit of the polymers. Transverse electronic relaxation rates, measur ed by EPR, increase with increasing rotational correlation time. Rigid intr amolecular micellelike structures form in aqueous solutions of the Gd(DTPA- bis-amide)alkyl copolymers. Consequently, the longitudinal O-17 relaxation rates for [Gd(DTPA-BA)-(CH2)(10)](x) and [Gd(DTPA-BA)-(CH2)(12)](x), were i nterpreted with the Lipari-Szabo treatment. This involves the inclusion of a global correlation time, representing the motion of the whole micellelike association, and a local correlation time, representing the motion of the Gd-O vector. The global correlation time obtained for the two polymers refl ects the ratio of the molecular weights, whereas the local correlation time s and the general order parameters are similar for both copolymers. The pro ton relaxivity difference can be explained by the different global correlat ion times. Thus, contrary to linear polymers in general, for the present po lymers the global motion significantly contributes to relaxivity. Relaxivit y is limited by water exchange; simulations show that proton relaxivities o ver 100 mM(-1)s(-1) could be obtained by substituting the Gd(DTPA-bisamide) units with a gadolinium chelate with fast water exchange.