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64Cu-Labeled PEGylated Polyethylenimine for Cell Trafficking and Tumor Imaging



In this study, we exploited the potential of 64Cu-labeled polyethylenimine (PEI) for cell trafficking and tumor imaging as compared to copper-64-pyruvaldehyde-bis(N 4-methylthiosemicarbazone) (64Cu-PTSM).


U87MG cells were labeled with both 64Cu-PEI and 64Cu-PTSM, and their in vivo distributions in mice were tracked by positron emission tomography (PET). The tumor imaging ability of 64Cu-PTSM and 64Cu-PEI was investigated in U87MG human glioblastoma xenograft model. 64Cu-PEI-polyethylene glycol (PEG) was also synthesized, and the cell uptake, efflux, cytotoxicity, and the biodistribution were carried out and compared with 64Cu-PEI.


Both 64Cu-PEI and 64Cu-PEI-PEG were obtained in high labeling yield without the need of macrocyclic chelating agents. 64Cu-PEI showed lower cell labeling efficiency than 64Cu-PTSM. Small-animal PET images of living mice indicate that tail-vein-injected U87MG cells labeled with 64Cu-PTSM or 64Cu-PEI traffic to the lungs and liver. In a subcutaneous U87MG xenograft model, 64Cu-PEI had higher tumor uptake (18.7 ± 2.2 %ID/g at 24 h) than 64Cu-PTSM (12.4 ± 1.7 %ID/g at 24 h). In comparison with 64Cu-PEI, 64Cu-PEI-PEG had decreased toxicity and increased cell uptake in cell culture, as well as higher tumor uptake and better tumor-to-background contrast in U87MG xenograft model.


64Cu-labeled polyethylenimine can be used for both cell trafficking and tumor imaging. PEGylation reduces the toxicity of 64Cu-PEI and improves the tumor imaging ability.

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This work was supported by National Cancer Institute (NCI) (R01 CA119053, R21 CA121842, R21 CA102123, P50 CA114747, U54 CA119367, and R24 CA93862), and Department of Defense (DOD) (W81XWH-07-1-0374, W81XWH-04-1-0697, W81XWH-06-1-0665, W81XWH-06-1-0042, and DAMD17-03-1-0143). We also thank the cyclotron team at the University of Wisconsin, Madison for 64Cu production.

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Correspondence to Xiaoyuan Chen.

Additional information

Zi-Bo Li and Kai Chen contributed equally to this work.

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Li, Z., Chen, K., Wu, Z. et al. 64Cu-Labeled PEGylated Polyethylenimine for Cell Trafficking and Tumor Imaging. Mol Imaging Biol 11, 415 (2009). https://doi.org/10.1007/s11307-009-0228-x

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Key words

  • Cell trafficking
  • Polyethylenimine (PEI)
  • Tumor imaging
  • Positron emission tomography (PET)
  • 64Cu