Frontiers of Medicine

, Volume 11, Issue 1, pp 120–128 | Cite as

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

  • Yanlin Zhao
  • Xiao Zhong
  • Xiaohong Ou
  • Huawei Cai
  • Xiaoai Wu
  • Rui Huang
Research Article

Abstract

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.

Keywords

norepinephrine transporter vesicular monoamine transporter 2 131I-MIBG gene therapy lentivirus vector 

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Notes

Acknowledgements

We thank Yuanyou Yang, PhD, for helping in the preparation of 131I-MIBG. This study was funded by the National Natural Science Foundation of China (No. 81271602).

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Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Yanlin Zhao
    • 1
  • Xiao Zhong
    • 1
  • Xiaohong Ou
    • 1
  • Huawei Cai
    • 1
  • Xiaoai Wu
    • 1
  • Rui Huang
    • 1
  1. 1.Department of Nuclear Medicine, West China HospitalSichuan UniversityChengduChina

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