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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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Abstract

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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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant (grant no. 2012-013480) and the Basic Research Program of the KOSEF (grant no. R01-2006-000-10249-0) funded by the Korean government (MEST).

Conflicts of interest

None.

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Authors and Affiliations

  1. Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 75, Nowon-gil, Gongneung-dong, Nowon-gu, Seoul, 139-706, Korea

    Kwang Il Kim, Yong Jin Lee, Tae Sup Lee, Inho Song, Gi Jeong Cheon & Joo Hyun Kang

  2. Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

    Gi Jeong Cheon & Sang Moo Lim

  3. Department of Nuclear Medicine, Seoul National University College of Medicine, 28, Yongon-dong, Jongno-gu, Seoul, 110-744, Korea

    June-Key Chung

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  1. Kwang Il Kim
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Correspondence to June-Key Chung or Joo Hyun Kang.

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Kim, K.I., Lee, Y.J., Lee, T.S. et al. In Vitro Radionuclide Therapy and In Vivo Scintigraphic Imaging of Alpha-Fetoprotein-Producing Hepatocellular Carcinoma by Targeted Sodium Iodide Symporter Gene Expression. Nucl Med Mol Imaging 47, 1–8 (2013). https://doi.org/10.1007/s13139-012-0166-4

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  • DOI: https://doi.org/10.1007/s13139-012-0166-4

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