Cotransfecting norepinephrine transporter and vesicular monoamine transporter 2 genes for increased retention of metaiodobenzylguanidine labeled with iodine 131 in malignant hepatocarcinoma cells
10.1007/s11684-017-0501-3
- Author:
Zhao YANLIN
1
;
Zhong XIAO
;
Ou XIAOHONG
;
Cai HUAWEI
;
Wu XIAOAI
;
Huang RUI
Author Information
1. Department of Nuclear Medicine
- Keywords:
norepinephrine transporter;
vesicular monoamine transporter 2;
131I-MIBG;
gene therapy;
lentivirus vector
- From:
Frontiers of Medicine
2017;11(1):120-128
- CountryChina
- Language:Chinese
-
Abstract:
Norepinephrine transporter (NET) transfection leads to significant uptake of iodine-131-1abeled metaiodobenzylguanidine (131I-MIBG) in non-neuroendocrine tumors.However,the use of 131I-MIBG is limited by its short retention time in target cells.To prolong the retention of 131I-MIBG in target cells,we infected hepatocarcinoma (HepG2) cells with Lentivirus-encoding human NET and vesicular monoamine transporter 2 (VMAT2) genes to obtain NET-expressing,NET-VMAT2-coexpressing,and negative-control cell lines.We evaluated the uptake and efflux of 131I-MIBG both in vitro and in vivo in mice bearing transfected tumors.NET-expressing and NET-VMAT2-coexpressing cells respectively showed 2.24 and 2.22 times higher 131I-MIBG uptake than controls.Two hours after removal of 131I-MIBG-containing medium,25.4％ efflux was observed in NET-VMAT2-coexpressing cells and 38.6％ in NET-expressing cells.In vivo experiments were performed in nude mice bearing transfected tumors;results revealed that NET-VMAT2-coexpressing tumors had longer 131I-MIBG retention time than NET-expressing tumors.Meanwhile,NET-VMAT2-coexpressing and NET-expressing tumors displayed 0.54％ and 0.19％,respectively,of the injected dose per gram of tissue 24 h after 131I-MIBG administration.Cotransfection of HepG2 cells with NET and VMAT2 resulted in increased 131I-MIBG uptake and retention.However,the degree of increase was insufficient to be therapeutically effective in target cells.
