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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.

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  • 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.

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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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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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