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

Abstract

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.

• Authors: Zi-Bo Li, Kai Chen, Zhanhong Wu, Hui Wang, Gang Niu, Xiaoyuan Chen
• Journal: Molecular imaging and biology (Mol Imaging Biol) 2009 Nov-Dec Vol. 11 Issue 6 Pg. 415-23 ISSN: 1860-2002 [Electronic] United States
• PMID: 19430846 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Copper Radioisotopes
• Radiopharmaceuticals
• Tetrazolium Salts
• Thiazoles
• Polyethylene Glycols
• Polyethyleneimine
• thiazolyl blue

Topics

• Animals
• Cell Line, Tumor
• Cell Movement
• Copper Radioisotopes (chemistry)
• Glioblastoma (diagnostic imaging, pathology)
• Humans
• Isotope Labeling (methods)
• Kinetics
• Male
• Mice
• Mice, Nude
• Neoplasms (diagnostic imaging, pathology)
• Polyethylene Glycols (chemical synthesis, chemistry)
• Polyethyleneimine (chemical synthesis, chemistry)
• Positron-Emission Tomography (instrumentation, methods)
• Radiopharmaceuticals (chemistry)
• Tetrazolium Salts (metabolism)
• Thiazoles (metabolism)
• Xenograft Model Antitumor Assays