Cu-labeled PEGylated polyethylenimine for cell trafficking and tumor imaging

Purpose: In this study, we exploited the potential of Cu- labeled polyethylenimine (PEI) for cell trafficking and tumor imaging as compared to copper-64-pyruvaldehyde-bis(N -methylthiosemicarbazone) (Cu-PTSM). Procedures: U87MG cells were labeled with both Cu-PEI and Cu-PTSM, and their in vivo distributions in mice were tracked by positron emission tomography (PET). The tumor imaging ability of Cu-PTSM and Cu-PEI was investigated in U87MG human glioblastoma xenograft model. Cu-PEI-polyethylene glycol (PEG) was also synthesized, and the cell uptake, efflux, cytotoxicity, and the biodistribution were carried out and compared with Cu-PEI. Results: Both Cu-PEI and Cu-PEI-PEG were obtained in high labeling yield without the need of macrocyclic chelating agents. Cu-PEI showed lower cell labeling efficiency than Cu-PTSM. Small-animal PET images of living mice indicate that tail-vein-injected U87MG cells labeled with Cu-PTSM or Cu-PEI traffic to the lungs and liver. In a subcutaneous U87MG xenograft model, Cu-PEI had higher tumor uptake (18.7±2.2 %ID/g at 24 h) than Cu-PTSM (12.4±1.7 %ID/g at 24 h). In comparison with Cu-PEI, 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: Cu-labeled polyethylenimine can be used for both cell trafficking and tumor imaging. PEGylation reduces the toxicity of Cu-PEI and improves the tumor imaging ability. © Academy of Molecular Imaging 2009.