Orally Administered Manganese With and Without Ascorbic Acid as a Liver-Specific Contrast Agent and Bowel Marker for Magnetic Resonance Imaging

Abstract

The objectives of this clinical trial of orally administered manganese in magnetic resonance imaging (MRI) of the liver were to assess signal enhancements in the liver with and without the addition of an uptake promoter, ascorbic acid, and to evaluate acute safety. A total of 18 healthy adult males were enrolled in the present trial. Contrast medium: MnCl2, doses: 25, 50, and 100 micromoL/kg bw, respectively, and promoting agent: Ascorbic acid, doses: 50, 100, and 200 micromoL/kg bw, respectively, were used. All imaging was performed on a 1.5 T clinical MRI system. Three pulse-sequences in the abdomen were used: (1) T1-weighted axial gradient-echo (GRE), (2) T1-weighted coronal gradient-echo, and (3) T1-weighted axial spin-echo (SE). Time-points for imaging were precontrast, 1 hour, 2.5, 4, 6, 9, and 24 hours after MnCl2 intake. Safety parameters assessed were clinical examinations and vital signs, including heart rate and blood pressure. Hematology and clinical chemistry were assessed with standard laboratory procedures. All pulse-sequences showed a clear dose-response in liver-enhancement. Temporally, high enhancements in the liver were seen between 2.5 and 6 hours after MnCl2 intake. At the manganese dose 50-micromoL/kg bw, with ascorbic acid and at the dose 100-micromoL/kg bw, both with and without ascorbic acid, the hepatic enhancements were higher than 100% with the GRE pulse-sequence. The promoting effect of ascorbic acid was significant at a manganese-dose of 100-micromoL/kg bw. The contrast media distributed well in the small intestine, delineating intra-abdominal organs well. No serious or unexpected adverse events were encountered. The drug was generally well tolerated, except for minor gastrointestinal adverse events. No significant alteration in hematology or clinical chemistry was seen. Oral manganese is easy to use, and has few side effects. Besides the liver-specific effect, an additional benefit is the delineation of the intestine.