Synthesis,Characterization, and Biodistribution of a Dinuclear Gadolinium Complex with Improved Properties as a 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 ¹⁷O transverse relaxation rate versus temperature, and 4) a transmetallation assay. In vivo biodistribution MRI studies at 1 T 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 (～20 mm ^?1 s^?1, 20 MHz, 310 K) 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.