A multinuclear MR study of Gd-EOB-DTPA: Comprehensive preclinical characterization of an organ specific MRI contrast agent

The characterization of the hepatobiliary contrast agent Gd-EOB-DTPA (gadolinium 3, 6, 9-triaza-3, 6, 9-tris(carboxymethyl)-4-(4-ethoxybenzyl)-undecandicarboxylic acid) in various media (water solution, protein containing solution, phosphorylated metabolites solution, and excised and perfused liver) was performed using different NMR approaches: water H-1 nuclear magnetic relaxation dispersion profiles, H-2 NMR longitudinal and transverse relaxation rates of labeled complex, water O-17 transverse relaxation rates and chemical shifts, P-31 relaxation rates and peak area of phosphorylated metabolites, The higher proton relaxivity of Gd-EOB-DTPA in water compared with Gd-DTPA is related to a shorter distance (r) between the water proton and the gadolinium ion and to a [anger rotational correlation time (tau(R)) of the hydrated complex, Although the thermodynamic stability of Gd-EOB-DTPA is identical to the one of Gd-DTPA, its kinetic stability in solutions containing phosphorylated metabolites (ATP, phosphocreatine, and inorganic phosphate) as measured by P-31 relaxation rates analysis is higher than for the parent compound. Gd-EOB-DTPA binds noncovalently to serum proteins, Its interaction with human serum albumin is characterized by a dissociation constant of 1-4.1 mM as calculated from proton and deuterium relaxation rates and equilibrium dialysis, This noncovalent interaction involves the subdomain IIA of human serum albumin. P-31 spectroscopy of the excised and perfused rat livers was used to monitor the uptake of Gd-EOB-DTPA by the hepatocytes where it enhances the nuclear relaxation of the intracellular metabolites without impairing the adenosine triphosphate metabolism of the cells.