Norepinephrine transporter （NET） transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine （^131I-MIBG） in non-neuroendocrine tumors. However, the use of ^131I-MIBG is limited by its s...Norepinephrine transporter （NET） transfection leads to significant uptake of iodine-131-labeled 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.展开更多
基金We thank Yuanyou Yang, PhD, for helping in the preparation of ^131I- MIBG. This study was fimded by the National Natural Science Foundation of China （No. 81271602）.
文摘Norepinephrine transporter （NET） transfection leads to significant uptake of iodine-131-labeled 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.
