MRI Measurement of Hepatocyte Toxicity Using the New MRI Contrast Agent Manganese Dipyridoxal Diphosphate, a Manganese/Pyridoxal 5-Phosphate Chelate

This study reports the first in vivo results using an MR contrast agent manganese dipyridoxal diphosphate (Mn‐DPDP) designed to estimate the functional status of the hepatocyte. Thirty New Zealand white rabbits were studied in groups of 5 as follows: No. 1, control, MRI scans only; No. 2 MRI before and up to 90 min following 50 μmol/kg of Mn‐DPDP iv; No. 3, rabbits received 9.3 g ethanol/kg and MRI; No. 4, as in No. 3 but following Mn‐DPDP; No. 5, MRI as in No. 2 but 18 h. following 1000 mg/kg Dgalactosamine used to induce hepatocyte necrosis; and No. 6, rabbits received D‐galactosamine and Mn‐DPDP. In this study significant ethanol‐and D‐galactosamine‐induced hepatocyte damage was indicated by the increased SGPT serum levels in the rabbit. The use of Mn‐DPDP allowed detection of early hepatocyte necrosis in these animals whereas conventional spin‐echo MRI did not. The fact that D‐galactosamine curves with and without Mn‐DPDP were not significantly different indicated virtually no membrane transport or metabolism of Mn‐DPDP in the liver. Ethanol curves were not normal, but there was still considerable residual Mn‐DPDP metabolism. Mn‐DPDP appears to be an attractive agent in assessing hepatocyte function. © 1989 Academic Press, Inc.