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

Hyeona Yim; Su Geun Yang; Yong Sun Jeon; In Suh Park; Mina Kim; Don Haeng Lee; You Han Bae; Kun Na

doi:10.1016/j.biomaterials.2011.03.069

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

Hyeona Yim
, Su Geun Yang
, Yong Sun Jeon
, In Suh Park
, Mina Kim
, Don Haeng Lee
, You Han Bae
, Kun Na

The Catholic University of Korea
Utah-Inha DDS and Advanced Therapeutics
Inha University
University of Utah

Research output: Contribution to journal › Article › peer-review

67 Scopus citations

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. 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±8.9μM, 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.

Original language	English
Pages (from-to)	5187-5194
Number of pages	8
Journal	Biomaterials
Volume	32
Issue number	22
DOIs	https://doi.org/10.1016/j.biomaterials.2011.03.069
State	Published - Aug 2011

Bibliographical note

Funding Information:
This research was financially supported by the Fundamental R&D Program for Core Technology of Materials, Republic of Korea , the Gyeonggi Regional Research Center (GRRC) , the Ministry of Knowledge Economy (MKE) , and the Korea Industrial Technology Foundation (KOTEF) through the Human Resource Training Project for Strategic Technology, by the Catholic University of Korea, Research Fund, 2011.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Gadolinium
Hepatocyte-specific contrast agent
Liver cancer
MRI
Pullulan
T contrast

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10.1016/j.biomaterials.2011.03.069

Cite this

@article{0f18eaa68c0b43a18ee7eb6cd3fc6cd5,

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{\textregistered}) 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. 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±8.9μM, 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.",

keywords = "Gadolinium, Hepatocyte-specific contrast agent, Liver cancer, MRI, Pullulan, T contrast",

author = "Hyeona Yim and Yang, \{Su Geun\} and Jeon, \{Yong Sun\} and Park, \{In Suh\} and Mina Kim and Lee, \{Don Haeng\} and Bae, \{You Han\} and Kun Na",

note = "Funding Information: This research was financially supported by the Fundamental R\&D Program for Core Technology of Materials, Republic of Korea , the Gyeonggi Regional Research Center (GRRC) , the Ministry of Knowledge Economy (MKE) , and the Korea Industrial Technology Foundation (KOTEF) through the Human Resource Training Project for Strategic Technology, by the Catholic University of Korea, Research Fund, 2011. ",

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

AU - Yim, Hyeona

AU - Yang, Su Geun

AU - Jeon, Yong Sun

AU - Park, In Suh

AU - Kim, Mina

AU - Lee, Don Haeng

AU - Bae, You Han

AU - Na, Kun

N1 - Funding Information: This research was financially supported by the Fundamental R&D Program for Core Technology of Materials, Republic of Korea , the Gyeonggi Regional Research Center (GRRC) , the Ministry of Knowledge Economy (MKE) , and the Korea Industrial Technology Foundation (KOTEF) through the Human Resource Training Project for Strategic Technology, by the Catholic University of Korea, Research Fund, 2011.

PY - 2011/8

Y1 - 2011/8

N2 - 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. 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±8.9μM, 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.

AB - 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. 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±8.9μM, 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.

KW - Gadolinium

KW - Hepatocyte-specific contrast agent

KW - Liver cancer

KW - MRI

KW - Pullulan

KW - T contrast

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AN - SCOPUS:79956102075

SN - 0142-9612

VL - 32

SP - 5187

EP - 5194

JO - Biomaterials

JF - Biomaterials

IS - 22

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

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