Synthesis, characterization and biodistribution of a novel dinuclear gadolinium complex with improved properties as blood pool MRI agent.

A dinuclear gadolinium(III) chelate containing two moieties of diethylenetriaminepentaacetic acid (DTPA), covalently conjugated to an analogue of deoxycholic acid, was synthesized and thoroughly characterized. A full relaxometric analysis was carried out, consisting of 1)the acquisition of nuclear magnetic resonance dispersion (NMRD) profiles in various media; 2)the study of binding affinity to serum albumin; 3)the measurement of O-17 transverse relaxation rate versus temperature, and 4)a transmetallation assay. In vivo biodistribution MRI studies at 1T and blood pharmacokinetics assays were carried out in comparison with Gd-DTPA (Magnevist) and gadocoletic acid trisodium salt (B22956/1), two well-known Gd complexes that share the same chelating cage and the same deoxycholic acid residue of the Gd complex investigated herein ((GdDTPA)(2)-Chol). High affinity for plasma protein and, in particular, the availability of more than one binding site, allows the complex to reach a fairly high relaxivity value in plasma (approximate to 20mm(-1)s(-1), 20MHz, 310K) as well as to show unexpectedly enhanced properties of blood pooling, with an elimination half-life in rats approximately seven times longer than that of B22956/1.