title: Radioiodine gene therapy of hepatocellular carcinoma targeted human alpha fetoprotein.
abstract: BACKGROUND
  We conducted a molecular imaging and gene therapy method in alpha-fetoprotein (AFP)-producing hepatocellular carcinoma (HCC) by tumor-specific expression of the human sodium/iodide symporter (hNIS) using an AFP promoter.
  
  
  METHODS
  The tumor-specific expression of hNIS gene by the AFP enhancer/promoter was constructed as pcDNA3-AFP/hNIS. The pcDNA3-AFP/hNIS was stably transfected to human HCC (Huh-7/AN) and rat glioma cells (C6/AN). Functional hNIS expression was confirmed by radioiodine uptake. The mRNA and protein-expression level of hNIS were measured. Biodistribution of 131I was evaluated, and scintigraphic images of 99mTc were obtained in xenografted mice. A clonogenic assay was performed by 131I. And, the in vivo therapeutic effect of 131I was evaluated in xenografted mice.
  
  
  RESULTS
  In Huh-7/AN cells, iodine was highly accumulated and completely blocked by perchlorate. The protein and mRNA expression levels were correlated with iodine uptake. Radioiodine uptake in Huh-7/AN tumors was higher than those of control tumors and clearly visualized. The survival rate was significantly decreased in Huh-7/AN cells by 131I. Moreover, a growth of Huh-7/AN tumors was inhibited by 131I in mice.
  
  
  CONCLUSIONS
  AFP-producing hepatoma can be targeted and treated with radionuclides and hNIS, using AFP enhancer/promoter. This targeted hNIS gene therapy and molecular imaging have the potential to be used in the management of AFP-producing HCC.
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yong Nan
authors.initials: YN
authors.lastname: Jin
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Chung
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Kang
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Kwang Il
authors.initials: KI
authors.lastname: Kimm
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Kim
authors.forename: Seunghoo
authors.initials: S
authors.lastname: Kim
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000532:radiotherapy* / Q000628:therapy*; D045744:Cell Line, Tumor; D004742:Enhancer Elements, Genetic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000532:radiotherapy* / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D051381:Rats; D013667:Technetium / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000096:biosynthesis*
chemical_list: D007457:Iodine Radioisotopes; D000509:alpha-Fetoproteins; D013667:Technetium