S-Space College of Medicine/School of Medicine (의과대학/대학원) Nuclear Medicine (핵의학전공) Journal Papers (저널논문_핵의학전공)
Radioiodine gene therapy of hepatocellular carcinoma targeted human alpha fetoprotein
- Jin, Yong Nan; Chung, Hye Kyung; Kang, Joo Hyun; Lee, Yong Jin; Kimm, Kwang Il; Kim, Young Joo; Kim, Seunghoo; Chung, June-Key
- Issue Date
- Mary Ann Liebert
- Cancer Biother Radiopharm. 2008;23(5):551-560
- Animals; Carcinoma, Hepatocellular/*radiotherapy/*therapy; Cell Line, Tumor; Enhancer Elements, Genetic; Gene Therapy/*methods; Humans; Iodine Radioisotopes/*pharmacology; Liver Neoplasms/*radiotherapy/*therapy; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Promoter Regions, Genetic; Rats; Technetium/metabolism; alpha-Fetoproteins/*biosynthesis
- INTRODUCTION: 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.
- 1557-8852 (Electronic)
- Files in This Item: There are no files associated with this item.