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


METHODS
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.


CONCLUSIONS
(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.
Li
Zi-Bo
ZB
Department of Radiology and Bio-X Program, Stanford University School of Medicine, Stanford, CA, USA.
Chen
Kai
K
Wu
Zhanhong
Z
Wang
Hui
H
Niu
Gang
G
Chen
Xiaoyuan
X
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D003301:Copper Radioisotopes / Q000737:chemistry*; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods; D019275:Radiopharmaceuticals / Q000737:chemistry*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D003301:Copper Radioisotopes; D019275:Radiopharmaceuticals; D013778:Tetrazolium Salts; D013844:Thiazoles; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; C022616:thiazolyl blue