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Molecular Imaging and Biology

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01-11-2009 | Research Article

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

Authors: Zi-Bo Li, Kai Chen, Zhanhong Wu, Hui Wang, Gang Niu, Xiaoyuan Chen

Published in: Molecular Imaging and Biology | Issue 6/2009

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.

Guerra-Crespo M, Charli JL, Rosales-Garcia VH, Pedraza-Alva G, Perez-Martinez L (2003) Polyethylenimine improves the transfection efficiency of primary cultures of post-mitotic rat fetal hypothalamic neurons. J Neurosci Methods 127:179–192CrossRefPubMed

Aoki K, Furuhata S, Hatanaka K et al (2001) Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in the murine peritoneal cavity. Gene Ther 8:508–514CrossRefPubMed

Suk JS, Suh J, Choy K, Lai SK, Fu J, Hanes J (2006) Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles. Biomaterials 27:5143–5150CrossRefPubMed

Zou SM, Erbacher P, Remy JS, Behr JP (2000) Systemic linear polyethylenimine (L-PEI)-mediated gene delivery in the mouse. J Gene Med 2:128–134CrossRefPubMed

Khin C, Lim MD, Tsuge K, Iretskii A, Wu G, Ford PC (2007) Amine nitrosation via NO reduction of the polyamine copper(II) complex Cu(DAC)²⁺. Inorg Chem 46:9323–9331CrossRefPubMed

Wojciechowska A, Bolewski L, Lomozik L (1991) A study of polyamine complex formation with H⁺, Cu(II), Zn(II), Pb(II), and Mg(II) in aqueous solution. Monatsh Chem 122:131–138CrossRef

Doyle B, Kemp BJ, Chareonthaitawee P et al (2007) Dynamic tracking during intracoronary injection of ¹⁸F-FDG-labeled progenitor cell therapy for acute myocardial infarction. J Nucl Med 48:1708–1714CrossRefPubMed

Adonai N, Nguyen KN, Walsh J et al (2002) Ex vivo cell labeling with ⁶⁴Cu-pyruvaldehyde-bis(N ⁴-methylthiosemicarbazone) for imaging cell trafficking in mice with positron-emission tomography. Proc Natl Acad Sci USA 99:3030–3035CrossRefPubMed

Blower PJ, Lewis JS, Zweit J (1996) Copper radionuclides and radiopharmaceuticals in nuclear medicine. Nucl Med Biol 23:957–980CrossRefPubMed

10.

Chen X, Conti PS, Moats RA (2004) In vivo near-infrared fluorescence imaging of integrin α_vβ₃ in brain tumor xenografts. Cancer Res 64:8009–8014CrossRefPubMed

11.

Li ZB, Cai W, Cao Q et al (2007) ⁶⁴Cu-labeled tetrameric and octameric RGD peptides for small-animal PET of tumor α_vβ₃ integrin expression. J Nucl Med 48:1162–1171CrossRefPubMed

12.

Wu Y, Zhang X, Xiong Z et al (2005) microPET imaging of glioma integrin α_vβ₃ expression using ⁶⁴Cu-labeled tetrameric RGD peptide. J Nucl Med 46:1707–1718PubMed

13.

Schiffelers RM, Ansari A, Xu J et al (2004) Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic Acids Res 32:e149CrossRefPubMed

14.

Chen D, Sun Y, Martell AE, Welch MJ (2002) Two novel macrocyclic monooxo-tetraamines and the stabilities of their Cu(II) complexes. Inorganica Chimica Acta 335:119–124CrossRef

15.

Kong D, Reibenspies J, Martell AE, Motekaitis RJ (2001) A new unsymmetrical polyamine macrocycle incorporating two phenolic functions: synthesis, basicity and coordination behavior toward copper(II). Inorganica Chimica Acta 324:35–45CrossRef

16.

Garnett MC (1999) Gene-delivery systems using cationic polymers. Crit Rev Ther Drug Carrier Syst 16:147–207PubMed

17.

Behr JP (1997) The proton sponge. A trick to enter cells the viruses did not exploit. Chimia 51:34–36

18.

Sonawane ND, Szoka FC Jr, Verkman AS (2003) Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes. J Biol Chem 278:44826–44831CrossRefPubMed

19.

Forrest ML, Pack DW (2002) On the kinetics of polyplex endocytic trafficking: implications for gene delivery vector design. Mol Ther 6:57–66CrossRefPubMed

20.

Petersen H, Fechner PM, Martin AL et al (2002) Polyethylenimine-graft-poly(ethylene glycol) copolymers: influence of copolymer block structure on DNA complexation and biological activities as gene delivery system. Bioconjug Chem 13:845–854CrossRefPubMed

21.

Moore NM, Barbour TR, Sakiyama-Elbert SE (2008) Synthesis and characterization of four-arm poly(ethylene glycol)-based gene delivery vehicles coupled to integrin and dna-binding peptides. Mol Pharm 5(1):140–150CrossRefPubMed

22.

Kim WJ, Yockman JW, Jeong JH et al (2006) Anti-angiogenic inhibition of tumor growth by systemic delivery of PEI-g-PEG-RGD/pCMV-sFlt-1 complexes in tumor-bearing mice. J Control Release 114:381–388CrossRefPubMed

23.

Temming K, Schiffelers RM, Molema G, Kok RJ (2005) RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature. Drug Resist Updat 8:381–402CrossRefPubMed

24.

Kunath K, Merdan T, Hegener O, Haberlein H, Kissel T (2003) Integrin targeting using RGD-PEI conjugates for in vitro gene transfer. J Gene Med 5:588–599CrossRefPubMed

25.

Chiu SJ, Ueno NT, Lee RJ (2004) Tumor-targeted gene delivery via anti-HER2 antibody (trastuzumab, Herceptin) conjugated polyethylenimine. J Control Release 97:357–369CrossRefPubMed

26.

Jeong JH, Lee M, Kim WJ et al (2005) Anti-GAD antibody targeted non-viral gene delivery to islet beta cells. J Control Release 107:562–570CrossRefPubMed

Title: 64Cu-Labeled PEGylated Polyethylenimine for Cell Trafficking and Tumor Imaging
Authors: Zi-Bo Li
Kai Chen
Zhanhong Wu
Hui Wang
Gang Niu
Xiaoyuan Chen
Publication date: 01-11-2009
Publisher: Springer-Verlag
Published in: Molecular Imaging and Biology / Issue 6/2009
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-009-0228-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

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