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Protein labeling with the labeling precursor [18F]SiFA-SH for positron emission tomography

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Abstract

Proteins previously derivatized with the cross-coupling reagent sulfo-SMCC (4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxy-succinimide ester sodium salt) can be easily labeled in high radiochemical yields with the silicon-fluoride acceptor (SiFA) reagent [18F]SiFA-SH, obtained via isotopic exchange, by thiol-maleimide coupling chemistry (n = 10). The specific activity of SiFA-SH obtained in a one-step labeling reaction was >18.5 GBq μmol−1 (>500 Ci mmol−1). The number of SiFA building blocks per protein molecule is defined by the previously introduced number of maleimide groups, which can be determined by a simple and convenient Ellman's assay. Not more than two maleimide groups are introduced using sulfo-SMCC, thereby keeping the modification of the protein low and preserving its biological activity.

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Figure 1: 18F Labeling of sulfo-SMCC-modified proteins using [18F]SiFA-SH ([18F]1).
Figure 2: HPLC chromatogram of [18F]SiFA-SH-labeled, sulfo-SMCC-derivatized RSA ([18F]4) after NAP-10 purification.

Change history

  • 23 October 2012

     In the version of this article initially published online, Katy Orchowski's name was spelled incorrectly. The surname Orchovski has been corrected to read Orchowski. The error has been corrected in all versions of this article.

References

  1. Kostikov, A.P. et al. Synthesis of [18F]SiFB: a prosthetic group for direct protein radiolabeling for application in positron emission tomography. Nat. Protoc. 7, 1956–1963 (2012).

    Article  CAS  Google Scholar 

  2. Wängler, C. et al. One-step 18F-labeling of peptides for positron emission tomography imaging using the SiFA methodology. Nat. Protoc. 7, 1946–1955 (2012).

    Article  Google Scholar 

  3. Wängler, C. et al. Protein based imaging agents for in vivo positron-emission-tomography: a universally applicable gallium-68 labeling technique. J. Nucl. Med. 52, 586–591 (2011).

    Article  Google Scholar 

  4. Ting, R., Adam, M.J., Ruth, T.J. & Perrin, D.M. Arylfluoroborates and alkylfluorosilicates as potential PET imaging agents: high-yielding aqueous biomolecular F-18-labeling. J. Am. Chem. Soc. 127, 13094–13095 (2005).

    Article  CAS  Google Scholar 

  5. Li, Y. et al. Towards kit-like 18F-labeling of marimastat, a noncovalent inhibitor drug for in vivo PET imaging cancer associated matrix metalloproteases. Med. Chem. Commun. 2, 942–949 (2011).

    Article  CAS  Google Scholar 

  6. Ting, R. et al. Toward [18F]-labeled aryltrifluoroborate radiotracers: in vivo positron emission tomography imaging of stable aryltrifluoroborate clearance in mice. J. Am. Chem. Soc. 130, 12045–12055 (2008).

    Article  CAS  Google Scholar 

  7. McBride, W.J. et al. A novel method of 18F radiolabeling for PET. J. Nucl. Med. 50, 991–998 (2009).

    Article  CAS  Google Scholar 

  8. McBride, W.J. et al. Improved 18F labeling of peptides with a fluoride-aluminum-chelate complex. Bioconjug. Chem. 21, 1331–1340 (2010).

    Article  CAS  Google Scholar 

  9. McBride, W.J., D'Souza, C.A., Sharkey, R.M. & Goldenberg, D.M. The radiolabeling of proteins by the [18F]AlF method. Appl. Radiat. Isot. 70, 200–204 (2012).

    Article  CAS  Google Scholar 

  10. Cai, L., Lu, S. & Pike, V.W. Chemistry with [18F]fluoride ion. Eur. J. Org. Chem. 2008, 2853–2873 (2008).

    Article  Google Scholar 

  11. Smith, G.E., Sladen, H.L., Biagini, C.G. & Blower, P.J. Inorganic approaches for radiolabeling biomolecules with fluorine-18 for imaging with positron emission tomography. Dalton Trans. 40, 6196–6205 (2001).

    Article  Google Scholar 

  12. Wu, Z. & Kandeel, F. 18F-labeled proteins. Curr. Pharm. Biotechnol. 11, 572–580 (2010).

    Article  CAS  Google Scholar 

  13. Wester, H.J. & Schottelius, M. Fluorine-18 labeling of peptides and proteins. Ernst Schering Res. Found. Workshop 62, 79–111 (2007).

    Article  CAS  Google Scholar 

  14. Vaidyanathan, G. & Zalutsky, M.R. Labeling proteins with fluorine-18 using N-succinimidyl 4-[18F]fluorobenzoate. Nucl. Med. Biol. 19, 275–281 (1992).

    CAS  Google Scholar 

  15. Brikh, A. & Morin, C. Boronated thiophenols: a preparation of 4-mercaptophenylboronic acid and derivatives. J. Organomet. Chem. 581, 82–86 (1999).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the cyclotron crew of the McConnell Brain Imaging Centre for providing fluorine-18. The financial support of the following grant agencies are gratefully acknowledged: Canada Foundation for Innovation project no. 203639 to R.S., Natural Sciences and Engineering Research Council of Canada (NSERC) Strategic Project Grant Program (STPGP) no. 412893 to R.S., Bayern-Quebec-Allianz to S.N., Deutsche Forschungsgemeinschaft (DFG) grant no. WA 2132/3-1 to B.W. and Fonds der Chemischen Industrie to C.W.

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A.P.K., S.N., J.C., K.O., E.S., L.I.-B., K.J. and C.W. performed the experimental work. R.S., C.W. and B.W. wrote the manuscript.

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Correspondence to Carmen Wängler or Ralf Schirrmacher.

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The authors declare no competing financial interests.

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Wängler, B., Kostikov, A., Niedermoser, S. et al. Protein labeling with the labeling precursor [18F]SiFA-SH for positron emission tomography. Nat Protoc 7, 1964–1969 (2012). https://doi.org/10.1038/nprot.2012.111

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