Nucl Med Mol Imaging.  2013 Mar;47(1):1-8.

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

• Kim KI
• Lee YJ
• Lee TS
• Song I
• Cheon GJ
• Lim SM
• Chung JK
• Kang JH

Abstract

PURPOSE
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 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.
RESULTS
The 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.
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.

Keyword

Hepatocellular carcinoma (HCC); Alpha-fetoprotein (AFP) promoter; Adenovirus; Tumor-targeted gene expression; Systemic delivery; Radioiodide therapy

MeSH Terms

Adenoviridae
alpha-Fetoproteins
Animals
Carcinoma, Hepatocellular
Gene Expression
Genes, vif
Genetic Therapy
Homicide
Humans
Ion Transport
Mice
Molecular Imaging
Polymerase Chain Reaction
Reverse Transcription
RNA, Messenger
Sodium
Sodium Iodide
Symporters
Transplantation, Heterologous
RNA, Messenger
Sodium
Sodium Iodide
Symporters
alpha-Fetoproteins