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 mumol/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 D-galactosamine 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.