Journal
BIOMATERIALS
Volume 32, Issue 22, Pages 5187-5194Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.03.069
Keywords
MRI; Liver cancer; Pullulan; T(1) contrast; Gadolinium; Hepatocyte-specific contrast agent
Funding
- Fundamental R&D Program for Core Technology of Materials, Republic of Korea
- Gyeonggi Regional Research Center (GRRC)
- Ministry of Knowledge Economy (MKE)
- Korea Industrial Technology Foundation (KOTEF)
- Catholic University of Korea
- Ministry of Knowledge Economy (MKE), Republic of Korea [2008-I08-028] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 (R)) 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. IC(50) 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 +/- 8.91 mu M, 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. (C) 2011 Elsevier Ltd. All rights reserved.
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