title: The performance of gadolinium diethylene triamine pentaacetate-pullulan hepatocyte-specific T1 contrast agent for MRI.
abstract: 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 24h. 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 ± 8.9 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.
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Hyeona
authors.initials: H
authors.lastname: Yim
authors.forename: Su-Geun
authors.initials: SG
authors.lastname: Yang
authors.forename: Yong Sun
authors.initials: YS
authors.lastname: Jeon
authors.forename: In Suh
authors.initials: IS
authors.lastname: Park
authors.forename: Mina
authors.initials: M
authors.lastname: Kim
authors.forename: Don Haeng
authors.initials: DH
authors.lastname: Lee
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
authors.forename: Kun
authors.initials: K
authors.lastname: Na
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism; D019786:Gadolinium DTPA / Q000737:chemistry / Q000378:metabolism; D005936:Glucans / Q000737:chemistry / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D015394:Molecular Structure; D051381:Rats
chemical_list: D037263:Asialoglycoprotein Receptor; D003287:Contrast Media; D005936:Glucans; C009109:pullulan; D019786:Gadolinium DTPA