Cotransfecting norepinephrine transporter and vesicular monoamine transporter 2 genes for increased retention of metaiodobenzylguanidine labeled with iodine 131 in malignant hepatocarcinoma cells

Cotransfecting norepinephrine transporter and vesicular monoamine transporter 2 genes for increased retention of metaiodobenzylguanidine labeled with iodine 131 in malignant hepatocarcinoma cells

Frontiers of Medicine, March 2017

28213878

Yanlin Zhao, Xiao Zhong, Xiaohong Ou, Huawei Cai, Xiaoai Wu, Rui Huang

Norepinephrine transporter (NET) transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine ((131)I-MIBG) in non-neuroendocrine tumors. However, the use of (131)I-MIBG is limited by its short retention time in target cells. To prolong the retention of (131)I-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 (131)I-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 (131)I-MIBG uptake than controls. Two hours after removal of (131)I-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 (131)I-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 (131)I-MIBG administration. Cotransfection of HepG2 cells with NET and VMAT2 resulted in increased (131)I-MIBG uptake and retention. However, the degree of increase was insufficient to be therapeutically effective in target cells.