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KMID : 1148920130470010001
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Nuclear Medicine and Molecular Imaging
2013 Volume.47 No. 1 p.1 ~ p.8
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In Vitro Radionuclide Therapy and In Vivo Scintigraphic Imaging of Alpha-Fetoprotein-Producing Hepatocellular Carcinoma by Targeted Sodium Iodide Symporter Gene Expression
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Kim Kwang-Il
Lee Yong-Jin
Lee Tae-Sup
Song In-Ho
Cheon Gi-Jeong
Lim Sang-Moo
Chung June-Key
Kang Joo-Hyun
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Abstract
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Purpose: This study aimed to develop a gene expression targeting method for specific imaging and therapy of alpha-fetoprotein (AFP)-producing hepatocellular carcinoma (HCC) cells, using an adenovirus vector containing the human sodium/iodide symporter (hNIS) gene driven by an AFP enhancer/promoter.
Methods: The recombinant adenovirus vector, AdAFPhNIS (containing the hNIS gene driven by human AFP enhancer/promoter) was prepared. After in vitro infection by the adenovirus, hNIS gene expression in AFP-producing cells and in AFP-nonproducing cells was investigated using 125I uptake assay and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The killing effect of 131I on AdAFPhNIS-infected HCC cells was studied using an in vitro clonogenic assay. In addition, tumor-bearing mice were intravenously injected with the adenovirus, and scintigraphic images were obtained.
Results: The expression of hNIS was efficiently demonstrated by 125I uptake assay in AFP-producing cells, but not in AFP-nonproducing cells. AFP-producing HCC-targeted gene expression was confirmed at the mRNA level. Furthermore, in vitro clonogenic assay showed that hNIS gene expression induced by AdAFPhNIS infection in AFP-producing cells caused more sensitivity to 131I than that in AFP-nonproducing cells. Injected intravenously in HuH-7 tumor xenografts mice by adenovirus, the functional hNIS gene expression was confirmed in tumor by in vivo scintigraphic imaging.
Conclusions: An AFP-producing HCC was targeted with an adenovirus vector containing the hNIS gene using the AFP enhancer/promoter in vitro and in vivo. These findings demonstrate that AFP-producing HCC-specific molecular imaging and radionuclide gene therapy are feasible using this recombinant adenovirus vector system.
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KEYWORD
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Hepatocellular carcinoma (HCC), Alpha-fetoprotein (AFP) promoter, Adenovirus, Tumor-targeted gene expression, Systemic delivery, Radioiodide therapy
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