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Radioiodine gene therapy of hepatocellular carcinoma targeted human alpha fetoprotein

Cited 7 time in Web of Science Cited 7 time in Scopus
Authors
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
2008-11-07
Publisher
Mary Ann Liebert
Citation
Cancer Biother Radiopharm. 2008;23(5):551-560
Keywords
AnimalsCarcinoma, Hepatocellular/*radiotherapy/*therapyCell Line, TumorEnhancer Elements, GeneticGene Therapy/*methodsHumansIodine Radioisotopes/*pharmacologyLiver Neoplasms/*radiotherapy/*therapyMaleMiceMice, Inbred BALB CNeoplasm TransplantationPromoter Regions, GeneticRatsTechnetium/metabolismalpha-Fetoproteins/*biosynthesis
Abstract
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.
ISSN
1557-8852 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18986218

https://hdl.handle.net/10371/67758
DOI
https://doi.org/10.1089/cbr.2008.0467

https://doi.org/10.1089/cbr.2008.0467
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College of Medicine/School of Medicine (의과대학/대학원)Nuclear Medicine (핵의학전공)Journal Papers (저널논문_핵의학전공)
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