Dynamic evaluation of the hepatic uptake and clearance of manganese-based MRI contrast agents: A P-31 NMR study on the isolated and perfused rat liver

This spectroscopic study compares the mechanisms of the hepatic uptake of m anganese chloride (MnCl2) and manganese dipyridoxyl diphosphate (MnDPDP). A lterations of the phosphorus-31 (P-31)-NMR spectrum of the intracellular ad enosine 5'-triphosphate (ATP) are used to monitor the internalization of ma nganese by the isolated and perfused rat liver. Mn2+ delivered as MnCl2 in the perfusate rapidly enters the hepatocytes, where it strongly interacts w ith ATP, inducing a broadening of the 31P lines, The inhibition of the proc ess by nifedipine confirms that manganese ions cross the cellular membrane at least partly through Ca2+ channels, MnDPDP induces weaker but still sign ificant changes of the ATP spectrum. The inability of pyridoxine to compete for the uptake of manganese confirms that the vitamin B-6 carrier is not i nvolved in the internalization process of the paramagnetic complex. Finally , preincubation of MnDPDP with blood does not increase the extent of the di ssociation. The alterations of the P-31 spectrum of the liver subsequent to the administration of MnDPDP are attributable to a fraction of free Mn2+ r eleased by the chelate and delivered to the hepatocytes.