In vitro and in vivo studies of adenovirus-mediated human norepinephrine transporter gene transduction to hepatocellular carcinoma

Abstract

The clinical value of 131I-MIBG for targeted imaging and targeted radiotherapy is limited to neural crest-derived tumors expressing human norepinephrine transporters (hNET) protein. To extend 131I-MIBG- targeted therapy to other nonexpressed hNET tumors, this study investigated the hNET expression in vitro and in vivo in HepG2 hepatoma mediated by recombinant adenovirus encoding the hNET gene (Ad-hNET). For this purpose, the HepG2 cells showed a 4.87-fold increase in 125I-MIBG uptake after infection with Ad-hNET, and the uptake of 125I-MIBG could be specifically inhibited by maprotiline. Immunohistological analysis, in vivo biological study and 131I-MIBG scintigraphic imaging also revealed the high expression of hNET protein in hepatoma. This in vitro and in vivo studies demonstrate the feasibility of hNET gene transfer, meditated by adenovirus vector, could extend to tumors other than those derived from the neural crest, which provides a sound foundation for further investigation of hepatocellular carcinoma-targeted radiotherapy mediated by adenovirus transfection with hNET gene. © 2011 Nature America, Inc.