The performance of gadolinium diethylene triamine pentaacetate-pullulan hepatocyte-specific T1 contrast agent for MRI

The magnetic resonance (MR) functionalities of pullulan-conjugated gadolinium diethylene triamine pentaacetate (Gd-DTPA-Pullulan) as a new hepatocyte-specific contrast agent were evaluated. Pullulan, which specifically accumulates on hepatocytes via asialoglycoprotein receptors, was chemically linked with Gd-DTPA. Gd-DTPA-Pullulan displayed three times greater contrast enhancement than Gd-DTPA-BMA (Omniscan®) in delayed MR imaging (MRI) on orthotopic rat hepatocarcinoma (HCC). This contrast effect lasted up to 24 h. In particular, Gd-DTPA-Pullulan displayed a discriminative MR contrast on the regenerative and malignant hepatic nodules sequentially observed during the progress of cirrhotic HCC. Approximately 50% of injected Gd-DTPA-Pullulan was eliminated via the hepato-biliary system. IC50 of Gd-DTPA-Pullulan on Chang liver cells was much higher than Gd-DTPA and Gd-DTPA-BMA (309.1 ± 11.2, 173.5 ± 15.5 and 49.4 ± 8.9 μM, respectively). Any significant toxicities of Gd-DTPA-Pullulan at the conventional dose on the rats weren’t detected on histology studies. Gd-DTPA-Pullulan worked as a hepatocyte-specific MR contrast agent with increased MR functionalities and an acceptable safety profile setting the scene for future clinical trials.