title: In vitro radionuclide therapy and in vivo scintigraphic imaging of alpha-fetoprotein-producing hepatocellular carcinoma by targeted sodium iodide symporter gene expression.
abstract: OBJECTIVE
  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 (125)I uptake assay and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The killing effect of (131)I 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 (125)I 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 (131)I 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.
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 75, Nowon-gil, Gongneung-dong, Nowon-gu, Seoul 139-706 Korea.
authors.forename: Kwang Il
authors.initials: KI
authors.lastname: Kim
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 75, Nowon-gil, Gongneung-dong, Nowon-gu, Seoul 139-706 Korea.
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 75, Nowon-gil, Gongneung-dong, Nowon-gu, Seoul 139-706 Korea.
authors.forename: Tae Sup
authors.initials: TS
authors.lastname: Lee
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 75, Nowon-gil, Gongneung-dong, Nowon-gu, Seoul 139-706 Korea.
authors.forename: Inho
authors.initials: I
authors.lastname: Song
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 75, Nowon-gil, Gongneung-dong, Nowon-gu, Seoul 139-706 Korea ; Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Gi Jeong
authors.initials: GJ
authors.lastname: Cheon
authors.affiliation: Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Sang Moo
authors.initials: SM
authors.lastname: Lim
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, 28, Yongon-dong, Jongno-gu, Seoul 110-744 Korea.
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 75, Nowon-gil, Gongneung-dong, Nowon-gu, Seoul 139-706 Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Kang
keywords: Adenovirus; Alpha-fetoprotein (AFP) promoter; Hepatocellular carcinoma (HCC); Radioiodide therapy; Systemic delivery; Tumor-targeted gene expression