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One-step 18F labeling of biomolecules using organotrifluoroborates

Nature Protocols volume 10, pages 1423–1432 (2015)Cite this article

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Abstract

Herein we present a general protocol for the functionalization of biomolecules with an organotrifluoroborate moiety so that they can be radiolabeled with aqueous 18F fluoride (18F−) and used for positron emission tomography (PET) imaging. Among the β+-emitting radionuclides, fluorine-18 (18F) is the isotope of choice for PET, and it is produced, on-demand, in many hospitals worldwide. Organotrifluoroborates can be 18F-labeled in one step in aqueous conditions via 18F–19F isotope exchange. This protocol features a recently designed ammoniomethyltrifluoroborate, and it describes the following: (i) a synthetic strategy that affords modular synthesis of radiolabeling precursors via a copper-catalyzed 'click' reaction; and (ii) a one-step 18F-labeling method that obviates the need for HPLC purification. Within 30 min, 18F-labeled PET imaging probes, such as peptides, can be synthesized in good chemical and radiochemical purity (>98%), satisfactory radiochemical yield of 20–35% (n > 20, non-decay corrected) and high specific activity of 40–111 GBq/μmol (1.1–3.0 Ci/μmol). The entire procedure, including the precursor preparation and 18F radiolabeling, takes 7–10 d.

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Figure 1
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Figure 5: HPLC chromatograms of Sep-Pak-purified 18F-AMBF3-TATE.
Figure 6: [18F]AMBF3-TATE shows specific uptake in AR42J xenografts (dotted ovals) and low uptake in normal tissues.

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Acknowledgements

This work was supported by the National Sciences and Engineering Research Council, and the Canadian Cancer Society Research Institute, with contributions from the intramural research program at National Institute of Biomedical Imaging and Bioengineering, US National Institutes of Health.

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Authors and Affiliations

  1. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA

    Zhibo Liu, Dale O Kiesewetter & Xiaoyuan Chen

  2. Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada

    Kuo-Shyan Lin, François Bénard & Maral Pourghiasian

  3. Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada

    David M Perrin

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Contributions

Z.L., D.M.P., K.-S.L., F.B. and X.C. conceived and designed this research; Z.L. and M.P. performed the experiments; Z.L., K.-S.L. and F.B. analyzed the data; and Z.L., D.M.P., D.O.K. and X.C. wrote the manuscript.

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Correspondence to Zhibo Liu, David M Perrin or Xiaoyuan Chen.

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Liu, Z., Lin, KS., Bénard, F. et al. One-step 18F labeling of biomolecules using organotrifluoroborates. Nat Protoc 10, 1423–1432 (2015). https://doi.org/10.1038/nprot.2015.090

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