title: MRI measurement of hepatocyte toxicity using the new MRI contrast agent manganese dipyridoxal diphosphate, a manganese/pyridoxal 5-phosphate chelate.
abstract: 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.
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, Stanford University Medical Center, California 94305.
authors.forename: S W
authors.initials: SW
authors.lastname: Young
authors.forename: B B
authors.initials: BB
authors.lastname: Simpson
authors.forename: A V
authors.initials: AV
authors.lastname: Ratner
authors.forename: C
authors.initials: C
authors.lastname: Matkin
authors.forename: E A
authors.initials: EA
authors.lastname: Carter
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D003287:Contrast Media; D004492:Edetic Acid / Q000031:analogs & derivatives*; D000431:Ethanol / Q000633:toxicity*; D005688:Galactosamine / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008107:Liver Diseases / Q000175:diagnosis* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008345:Manganese; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives*; D011817:Rabbits; D013997:Time Factors
chemical_list: D003287:Contrast Media; D000431:Ethanol; D008345:Manganese; D011732:Pyridoxal Phosphate; D005688:Galactosamine; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid