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Meeting ReportMultimodality and Non-radioactive Molecular Imaging: Oncology

Hepatocellular carcinoma targeted reporter gene expression using alpha-fetoprotein (AFP) enhancer/promoter in mouse model

KI Kim, JK Chung, JH Kang, TS Lee, YJ Lee, JJ Park, IH Song, GJ Cheon, CW Choi and SM Lim
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 1021;
KI Kim
1KIRAMS, Molecular Imaging Research Center, Seoul, South Korea
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JK Chung
2Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul, South Korea
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JH Kang
1KIRAMS, Molecular Imaging Research Center, Seoul, South Korea
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TS Lee
1KIRAMS, Molecular Imaging Research Center, Seoul, South Korea
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YJ Lee
1KIRAMS, Molecular Imaging Research Center, Seoul, South Korea
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JJ Park
1KIRAMS, Molecular Imaging Research Center, Seoul, South Korea
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IH Song
1KIRAMS, Molecular Imaging Research Center, Seoul, South Korea
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GJ Cheon
1KIRAMS, Molecular Imaging Research Center, Seoul, South Korea
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CW Choi
1KIRAMS, Molecular Imaging Research Center, Seoul, South Korea
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SM Lim
1KIRAMS, Molecular Imaging Research Center, Seoul, South Korea
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Abstract

1021

Objectives This study aims to develop reporter gene targeting method for AFP-producing hepatocellular carcinoma (HCC) specific imaging and therapy using adenovirus vector containing reporter gene driven by AFP enhancer/promoter.

Methods The recombinant adenovirus vectors, AdAFPfLuc and AdAFPhNIS (containing firefly luciferase gene and human sodium/iodide symporter gene, respectively, driven by human AFP enhancer/promoter) were prepared. After an in vitro infection by adenovirus, the expression of reporter genes was confirmed by luciferase assay, I-125 uptake assay and RT-PCR analysis in AFP-producing cells (HuH-7 and HepG2), and in AFP-nonproducing cells (SK-Hep-1, Chang, and C6). The tumor-bearing mice were intravenously injected with adenovirus, and bioluminescent and scintigraphic images were obtained.

Results The expression of fLuc or hNIS was demonstrated efficiently by luciferase assay or I-125 uptake assay in AFP-producing cells, but not in AFP-nonproducing cells. Tumor specific reporter gene expression was confirmed on mRNA level by RT-PCR analysis. Injected intravenously in HuH-7 tumor bearing mice, adenovirus drove expression of a functional fLuc or hNIS protein by only HuH-7 tumor and allowed marked luciferase or hNIS activity, whereas AdCMVLuc drove fLuc expression only in liver.

Conclusions AFP-producing HCC was targeted with adenovirus vector containing reporter gene using AFP enhancer/promoter in vitro and in vivo. These findings demonstrate that AFP-producing HCC specific molecular imaging are feasible using this recombinant adenovirus vector system.

  • © 2009 by Society of Nuclear Medicine
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Journal of Nuclear Medicine
Vol. 50, Issue supplement 2
May 2009
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Hepatocellular carcinoma targeted reporter gene expression using alpha-fetoprotein (AFP) enhancer/promoter in mouse model
KI Kim, JK Chung, JH Kang, TS Lee, YJ Lee, JJ Park, IH Song, GJ Cheon, CW Choi, SM Lim
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 1021;

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Hepatocellular carcinoma targeted reporter gene expression using alpha-fetoprotein (AFP) enhancer/promoter in mouse model
KI Kim, JK Chung, JH Kang, TS Lee, YJ Lee, JJ Park, IH Song, GJ Cheon, CW Choi, SM Lim
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 1021;
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