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To investigate whether dynamic and delayed magnetic resonance imaging (MRI) with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), a hepatobiliary MRI contrast agent, has potential for the differential diagnosis of experimental hepatic tumors.Twelve male rats received N-nitrosomorpholine solution as drinking water to induce hepatic tumors. After injection of Gd-EOB-DTPA, rats were subjected to dynamic and delayed MRI. The relative enhancement (RE) was calculated, and the time of the maximum RE (Tmax) was evaluated. After MRI, liver was histologically analyzed.One hundred sixty-three hepatic tumors 3-12 mm in diameter were induced after 18 weeks of treatment with 0.01 wt/vol% of N-nitrosomorpholine, and 81 of them were evaluated. The RE in hyperplastic nodules (HPNs) was significantly higher than that in moderately or poorly differentiated hepatocellular carcinomas (HCCs) in the late phase, whereas there was no significant difference in RE between well-differentiated HCCs and HPNs. The average Tmax in HPNs was about 13 minutes, whereas that of each differentiated HCCs was about 1 minute.It was possible to differentiate benign HPNs and malignant HCCs (especially well-differentiated HCCs) by evaluating the change of RE or comparison of Tmax with Gd-EOB-DTPA-enhanced MRI.

Kato N, Yokawa T, Tamura A, et al. Gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid interaction with clinical drugs in rats. Invest Radiol 2002;37:680–684. To investigate whether the hepatic enhancement characteristics of Gd-EOB-DTPA are influenced by the preapplication of a variety of commonly used clinical pharmaceuticals (eg, antibiotics, antineoplastic drugs, corticosteroids, antiarrhythmia drugs, antianxiety drugs, scopolamine, and xanthine derivatives). Eleven commercially available drugs (prednisolone, rifampicin, doxorubicin hydrochloride, cisplatin, propranolol hydrochloride, scopolamine butylbromide, theophylline, ampicillin, cefotaxime sodium, verapamil hydrochloride, and diazepam) were intravenously (IV) injected in rats at three to five times the clinical dose (n = 3 or 6 per drug). A control group of rats was given saline (n = 6). Gd-EOB-DTPA (25 μmol Gd/kg IV) was administered to rats 30 minutes after the injections of the clinical drugs. Liver MR imaging was performed with a 2.0 T animal imager before and up to 60 minutes after injection. Enhancement (ENH) (%) and area under the data from time versus enhancement curve (AUD) were calculated. Rifampicin was the only drug that significantly decreased the hepatic enhancement by Gd-EOB-DTPA. Both the maximum enhancement of the liver and the AUD were significantly reduced when rifampicin was preinjected. Preinjection of prednisolone, doxorubicin hydrochloride, cisplatin or propranolol hydrochloride yielded a slightly but significant increased maximum enhancement of the liver. Furthermore, the enhancement declined more slowly when these drugs were preadministered, yielding a large AUD. None of the other drugs showed a significant effect on hepatic enhancement. Rifampicin exerted a clinically significant decrease on hepatic enhancement by Gd-EOB-DTPA. Prednisolone, doxorubicin hydrochloride, cisplatin, or propranolol hydrochloride slightly but significantly increased the hepatic enhancement by Gd-EOB-DTPA.