Comparison of manganese biodistribution and MR contrast enhancement in rats after intravenous injection of MnDPDP and MnCl2

Abstract

Purpose: To compare the time course of the MR enhancing properties and biodistri-bution of manganese (Mn) in rats given i.v. Mn dipyridoxyl diphosphate (MnDPDP) or Mn chloride (MnCl2). Material and Methods: Twenty-four adult rats were injected i.v. with 5 μmol/kg MnDPDP or MnCl2, or with 0.5 ml/kg saline. High resolution T1-weighted MR imaging was performed during early (10 min), mid (2 h) and late (24 h) phases after injection. Mn concentrations in major organs were measured by using an ICP-AES technique, and correlated with MR findings. Results: Variable degrees of signal enhancement of major organs observed in MR images corresponded with the amount of Mn uptake after injection of MnDPDP or MnCl2. A prominently lower cardiac, pancreatic and hepatic uptake of Mn was seen at 10 min in rats injected with MnDPDP compared with those given MnCl2 and this was reflected in a difference in signal intensity (SI) in the MR images. At 2 h, the Mn content and SI in the major organs were similar with both MnDPDP and MnCl2. An overall Mn clearance was achieved at 24 h without any important organ retention, with kidney excretion of Mn seen only with MnDPDP. Conclusion: With both MnDPDP and MnCl2, the Mn uptake correlates with the SI enhancement in tissues. The reduced initial cardiac uptake of Mn after MnDPDP treatment compared to MnCl2 may account for the favourable cardiovascular safety of the contrast agent. These data contribute to an understanding of SI enhancement by MnDPDP, and are consistent with other studies showing that at a dose of 5 μmol/kg, MnDPDP can be safely used as a potent MR organ-specific contrast agent.