EVIDENCE FOR THE DISSOCIATION OF THE HEPATOBILIARY MRI CONTRAST AGENTMN-DPDP

These experiments assessed and quantitated the release of free mangane se Mn++ from the hepatobiliary contrast agent Mn-DPDP (manganese dipyr idoxal 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 a queous solutions induced the release of Mn++ from the complex, as did incubation of the complex in liver homogenates. After intravenous inje ction of 15 mu mol/kg of Mn-DPDP, both EPR and P-31-NMR spectroscopy d emonstrated that Mn-DPDP is partly dissociated (approximately 25%) in the liver. By comparing in vitro and ex vivo data from the liver, we c oncluded that the dissociation,of Mn-DPDP occurs primarily in the live r, whereas a minor portion of the dissociated Mn found in the liver co mes from dissociation of the complex in the blood. Most of the dissoci ated Mn in liver becomes bound to macromolecules and is responsible fo r the enhancement of relaxivity observed with this agent.