In Vitro Radionuclide Therapy and In Vivo Scintigraphic Imaging of Alpha-Fetoprotein-Producing Hepatocellular Carcinoma by Targeted Sodium Iodide Symporter Gene Expression View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-09-06

AUTHORS

Kwang Il Kim, Yong Jin Lee, Tae Sup Lee, Inho Song, Gi Jeong Cheon, Sang Moo Lim, June-Key Chung, Joo Hyun Kang

ABSTRACT

PurposeThis 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.MethodsThe 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.ResultsThe 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.ConclusionsAn 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. More... »

PAGES

1-8

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URI

http://scigraph.springernature.com/pub.10.1007/s13139-012-0166-4

DOI

http://dx.doi.org/10.1007/s13139-012-0166-4

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https://app.dimensions.ai/details/publication/pub.1026960807

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24895502


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