64Cu-labeled PEGylated polyethylenimine for cell trafficking and tumor imaging.

PURPOSE: In this study, we exploited the potential of (64)Cu-labeled polyethylenimine (PEI) for cell trafficking and tumor imaging as compared to copper-64-pyruvaldehyde-bis(N (4)-methylthiosemicarbazone) ((64)Cu-PTSM). PROCEDURES: U87MG cells were labeled with both (64)Cu-PEI and (64)Cu-PTSM, and their in vivo distributions in mice were tracked by positron emission tomography (PET). The tumor imaging ability of (64)Cu-PTSM and (64)Cu-PEI was investigated in U87MG human glioblastoma xenograft model. (64)Cu-PEI-polyethylene glycol (PEG) was also synthesized, and the cell uptake, efflux, cytotoxicity, and the biodistribution were carried out and compared with (64)Cu-PEI.
RESULTS: Both (64)Cu-PEI and (64)Cu-PEI-PEG were obtained in high labeling yield without the need of macrocyclic chelating agents. (64)Cu-PEI showed lower cell labeling efficiency than (64)Cu-PTSM. Small-animal PET images of living mice indicate that tail-vein-injected U87MG cells labeled with (64)Cu-PTSM or (64)Cu-PEI traffic to the lungs and liver. In a subcutaneous U87MG xenograft model, (64)Cu-PEI had higher tumor uptake (18.7 +/- 2.2 %ID/g at 24 h) than (64)Cu-PTSM (12.4 +/- 1.7 %ID/g at 24 h). In comparison with (64)Cu-PEI, (64)Cu-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: (64)Cu-labeled polyethylenimine can be used for both cell trafficking and tumor imaging. PEGylation reduces the toxicity of (64)Cu-PEI and improves the tumor imaging ability.