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

Abstract Purpose  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). Procedures  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. Results  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. Conclusion   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. [ABSTRACT FROM AUTHOR]