Evidence for the dissociation of the hepatobiliary MRI contrast agent Mn-DPDP

These experiments assessed and quantitated the release of free manganese Mn++ from the hepatobiliary contrast agent Mn-DPDP (manganese dipyridoxal diphosphate), using several magnetic resonance techniques (EPR spectroscopy, P-31-NMR spectroscopy, and relaxometry) to differentiate between free Mn++ and Mn++ in complexes in various preparations. The presence of calcium and magnesium in physiological concentrations in aqueous solutions induced the release of Mn++ from the complex, as did incubation of the complex in liver homogenates. After intravenous injection of 15 mu mol/kg of Mn-DPDP, both EPR and P-31-NMR spectroscopy demonstrated that Mn-DPDP is partly dissociated (approximately 25%) in the liver. By comparing in vitro and ex vivo data from the liver, we concluded that the dissociation,of Mn-DPDP occurs primarily in the liver, whereas a minor portion of the dissociated Mn found in the liver comes from dissociation of the complex in the blood. Most of the dissociated Mn in liver becomes bound to macromolecules and is responsible for the enhancement of relaxivity observed with this agent.