Because the manganese-based contrast agents used in magnetic, resonance imaging are unstable in vivo, some concern exists about the potential toxicity coming from the Mn2+ released by the complexes. This potential problem arises because the manganese is known to accumulate in the brain of people intoxicated by this metal (manganism): this central accumulation leads to neurological disorders (i.e., parkinsonism-like syndrome). The aim of this study was to assess the amount of Mn found in the brain after administration of MnCl2 or different chelates of Mn in normal mice as well as in mice with impaired biliary elimination. Male NMRI mice received an intravenous injection in a caudal vein of 5 mumol/kg of 54Mn compounds as MnCl2, manganese-diethylenetriaminepentaacetate (Mn-DTPA), or manganese-dipyridoxal diphosphate (Mn-DPDP). The radiolabeled complexes (1:1) were prepared by direct chelation (Mn-DTPA) or transchelation of preformed complex (Mn-DPDP), and the radiochemical purity was assessed by paper chromatography. The mice were killed at various times post-exposure (0-3 months), and the radioactivity present in the organs was determined by gamma counting. For each compound analyzed in the present study, we observed an accumulation of Mn (0.25-0.3% of the amount injected/g of tissue) in the mouse brain, reaching a plateau after 24 h, while the Mn content in the liver was decreasing with time. The amount of Mn accumulated in the brain remained unchanged 1 month later, but decreased to 40% of the maximum amount 3 months after the exposure. In mice whose bile ducts had been ligated 24 h before the administration of the manganese compound, we observed, 1 week after the injection, an amount of manganese accumulated in the brain 2 times higher than in normal mice.

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Racemic 5-(4'-fluorophenyl)-5-phenylhydantoin was synthesized to examine its metabolism in rat. This compound differs from the antiepileptic agent 5,5-diphenylhydantoin in that the normal site of hydroxylation in 5,5-diphenylhydantoin is blocked on one of the phenyl groups by a fluorine atom. The 4'-fluoro analogue gives a major metabolite, which was isolated and identified as (R)-(-)-5-(4'-fluorophenyl)-5-(4'-hydroxyphenyl)hydantoin of 37% enantiomeric purity. The absolute configuration and enantiomeric purity of the metabolite was determined by chemical conversion to (S)-(-)-5-(4'-hydroxyphenyl)-5-phenylhydantoin. A second metabolite of the catechol type, possibly as a mixture of 5-(3',4'-dihydroxyphenyl)-5-(4'-fluorophenyl)hydantoin, and the corresponding O-3'-methyl derivative was detected by gas chromatography-mass spectrometry after methylation.