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

ABSTRACT

This spectroscopic study compares the mechanisms of the hepatic uptake of manganese chloride (MnCl2) and manganese dipyridoxyl diphosphate (MnDPDP). Alterations of the phosphorus-31 (31P)-NMR spectrum of the intracellular adenosine 5'-triphosphate (ATP) are used to monitor the internalization of manganese by the isolated and perfused rat liver. Mn2+ delivered as MnCl2 in the perfusate rapidly enters the hepatocytes, where it strongly interacts with ATP, inducing a broadening of the 31P lines. The inhibition of the process by nifedipine confirms that manganese ions cross the cellular membrane at least partly through Ca2+ channels. MnDPDP induces weaker but still significant changes of the ATP spectrum. The inability of pyridoxine to compete for the uptake of manganese confirms that the vitamin B6 carrier is not involved in the internalization process of the paramagnetic complex. Finally, preincubation of MnDPDP with blood does not increase the extent of the dissociation. The alterations of the 31P spectrum of the liver subsequent to the administration of MnDPDP are attributable to a fraction of free Mn2+ released by the chelate and delivered to the hepatocytes.