COMPARISON OF MANGANESE BIODISTRIBUTION AND MR CONTRAST ENHANCEMENT IN RATS AFTER INTRAVENOUS-INJECTION OF MNDPDP AND MNCL2

Purpose: To compare the time course of the MR enhancing properties and biodistribution of manganese (Mn) in rats given i.v. Mn dipyridoxyl d iphosphate (MnDPDP) or Mn chloride (MnCl2). Material and Methods: Twen ty-four adult rats were injected i.v. with 5 mu mol/kg MnDPDP or MnCl2 , or with 0.5 ml/kg saline. High resolution T1-weighted MR imag ing wa s performed during early (10 min), mid (2 h) and late (24 h) phases af ter injection. Mn concentrations in major organs were measured by usin g an ICP-AES technique, and correlated with MR findings. Results: Vari able degrees of signal enhancement of major organs observed in MR imag es 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 th ose given MnCl2 and this was reflected in a difference in signal inten sity (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 clearan ce was achieved at 24 h without any important organ retention, with ki dney excretion of Mn seen only with MnDPDP. Conclusion: With both MnDP DP and MnCl2, the Mn uptake correlates with the SI enhancement in tiss ues. The reduced initial cardiac uptake of Mn after MnDPDP treatment c ompared 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 mu mol/kg, MnDPDP can be safely used as a potent M R organ-specific contrast agent.