Skip to main content
SpringerLink
Log in

Preservation of Ligand Functionality by Click Chemistry

  • Chapter
  • First Online:
Radionanomedicine

Part of the book series: Biological and Medical Physics, Biomedical Engineering ((BIOMEDICAL))

  • 833 Accesses

Abstract

Click chemistry reactions have had a considerable impact in the effort to develop efficient synthetic strategies towards new radiopharmaceutical agents. This is largely due to the ability of these reactions to proceed rapidly under ambient conditions, resulting in an easily isolated product. These reaction properties are particularly desirable in the synthesis of positron emission tomography (PET) imaging agents containing short-lived radioisotopes, such as carbon-11 and fluorine-18. Striving to further improve on the suitability of these reactions, chemists have succeeded in developing new, streamlined click chemistry reactions with additional advantages. These versatile reactions have now been used extensively in the preparation of radiolabeled small molecules, peptides, proteins, and nanomaterials for nuclear imaging applications. A small number of these click chemistry reactions are also bioorthogonal as they have the ability to proceed efficiently and selectively within the complex biological medley of a living system. This rare and valuable attribute has led to their utilisation in pretargeted imaging strategies which have the potential to provide superior image quality and reduced radiation burden compared with conventional imaging approaches. In this chapter, we aim to introduce the click chemistry reactions which have had the greatest impact in the preparation of radiolabeled ligands for nuclear imaging applications, with special focus on the application of nanoparticles. In addition, we also describe the use of these reactions in combination with nanoparticle vectors to facilitate a pretargeted imaging strategy .

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. H.C. Kolb, M.G. Finn, K.B. Sharpless, Click chemistry: diverse chemical function from a few good reactions. Angew. Chem. Int. Ed. Engl. 40(11), 2004–2021 (2001)

    Article  Google Scholar 

  2. M. Meldal, C.W. Tornøe, Cu-catalyzed azide–alkyne cycloaddition. Chem. Rev. 108(8), 2952–3015 (2008)

    Article  Google Scholar 

  3. R. Huisgen, 1,3-dipolar cycloadditions. Past and future. Angew. Chem. Int. Ed. Engl. 2(10), 565–598 (1963)

    Article  Google Scholar 

  4. R. Huisgen, Kinetics and mechanism of 1,3-dipolar cycloadditions. Angew. Chem. Int. Ed. Engl. 2(11), 633–645 (1963)

    Article  Google Scholar 

  5. V.V. Rostovtsev, L.G. Green, V.V. Fokin, K.B. Sharpless, A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew. Chem. Int. Ed. Engl. 41(14), 2596–2599 (2002)

    Article  Google Scholar 

  6. C.W. Tornøe, C. Christensen, M. Meldal, Peptidotriazoles on solid phase:  [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J. Org. Chem. 67(9), 3057–3064 (2002)

    Article  Google Scholar 

  7. K. Nwe, M.W. Brechbiel, Growing applications of “click chemistry” for bioconjugation in contemporary biomedical research. Cancer Biother Radiopharm. 24(3), 289–302 (2009)

    Article  Google Scholar 

  8. C. Wängler, R. Schirrmacher, P. Bartenstein, B. Wängler, Click-chemistry reactions in radiopharmaceutical chemistry: fast & easy introduction of radiolabels into biomolecules for in vivo imaging. Curr. Med. Chem. 17(11), 1092–1116 (2010)

    Article  Google Scholar 

  9. T.L. Ross, M. Honer, P.Y.H. Lam, T.L. Mindt, V. Groehn, R. Schibli et al., Fluorine-18 click radiosynthesis and preclinical evaluation of a new 18F-labeled folic acid derivative. Bioconjug Chem. 19(12), 2462–2470 (2008)

    Article  Google Scholar 

  10. E. Galante, W.B. Schoultz, M. Koepp, E. Årstad, Chelator-accelerated one-pot ‘Click’ labeling of small molecule tracers with 2-[18F] fluoroethyl azide. Molecules 18(5) (2013)

    Article  Google Scholar 

  11. J. Marik, J.L. Sutcliffe, Click for PET: rapid preparation of [18F] fluoropeptides using CuI catalyzed 1,3-dipolar cycloaddition. Tetrahedron Lett. 47(37), 6681–6684 (2006)

    Article  Google Scholar 

  12. S.H. Hausner, J. Marik, M.K.J. Gagnon, J.L. Sutcliffe, In vivo positron emission tomography (PET) imaging with an αvβ6 specific peptide radiolabeled using 18F-“click” chemistry: evaluation and comparison with the corresponding 4-[18F] fluorobenzoyl- and 2-[18F] fluoropropionyl-peptides. J. Med. Chem. 51(19), 5901–5904 (2008)

    Article  Google Scholar 

  13. Z.-B. Li, Z. Wu, K. Chen, F.T. Chin, X. Chen, Click chemistry for 18F-labeling of RGD peptides and microPET imaging of tumor integrin αvβ3 expression. Bioconjug. Chem. 18(6), 1987–1994 (2007)

    Article  Google Scholar 

  14. T. Ramenda, R. Bergmann, F. Wuest, Synthesis of 18F-labeled neurotensin(8-13) via copper-mediated 1,3-dipolar [3+2] cycloaddition reaction. Lett. Drug Des. Discov. 4(4), 279–285 (2007)

    Article  Google Scholar 

  15. M. Glaser, E. Årstad, “Click labeling” with 2-[18F] fluoroethylazide for positron emission tomography. Bioconjug Chem. 18(3), 989–993 (2007)

    Article  Google Scholar 

  16. T. Ramenda, T. Kniess, R. Bergmann, J. Steinbach, F. Wuest, Radiolabeling of proteins with fluorine-18 via click chemistry. Chem. Commun (Camb) 48, 7521–7523 (2009)

    Article  Google Scholar 

  17. T. Ramenda, J. Steinbach, F. Wuest, 4-[18F] Fluoro-N-methyl-N-(propyl-2-yn-1-yl) benzenesulfonamide ([18F] F-SA): a versatile building block for labeling of peptides, proteins and oligonucleotides with fluorine-18 via Cu(I)-mediated click chemistry. Amino Acids 44(4), 1167–1180 (2013)

    Article  Google Scholar 

  18. N.K. Devaraj, E.J. Keliher, G.M. Thurber, M. Nahrendorf, R. Weissleder, 18F labeled nanoparticles for in vivo PET-CT imaging. Bioconjug. Chem. 20(2), 397–401 (2009)

    Article  Google Scholar 

  19. C.M. Lee, H.J. Jeong, D.W. Kim, M.H. Sohn, S.T. Lim, The effect of fluorination of zinc oxide nanoparticles on evaluation of their biodistribution after oral administration. Nanotechnology 23(20), 205102 (2012)

    Article  ADS  Google Scholar 

  20. C.D. Hein, X.-M. Liu, D. Wang, Click chemistry, a powerful tool for pharmaceutical sciences. Pharm. Res. 25(10), 2216–2230 (2008)

    Article  Google Scholar 

  21. T. Wang, Z. Guo. Copper in Medicine: Homeostasis, chelation therapy and antitumor drug design. Curr. Med. Chem. 13(5), 525–537 (2006)

    Article  MathSciNet  ADS  Google Scholar 

  22. K.D. Held, F.C. Sylvester, K.L. Hopcia, J.E. Biaglow, Role of fenton chemistry in thiol-induced toxicity and apoptosis. Radiat. Res. 145(5), 542–553 (1996)

    Article  ADS  Google Scholar 

  23. N.J. Agard, J.A. Prescher, C.R. Bertozzi, A strain-promoted [3+2] azide–alkyne cycloaddition for covalent modification of biomolecules in living systems. J. Am. Chem. Soc. 126(46), 15046–15047 (2004)

    Article  Google Scholar 

  24. G. Wittig, A. Krebs, Zur existenz niedergliedriger cycloalkine I. Chem. Ber. 94(12), 3260–3275 (1961)

    Article  Google Scholar 

  25. M.F. Debets, S.S. van Berkel, J. Dommerholt, A.J. Dirks, F.P.J.T. Rutjes, F.L. van Delft, Bioconjugation with strained alkenes and alkynes. Acc. Chem. Res. 44(9), 805–815 (2011)

    Article  Google Scholar 

  26. E.M. Sletten, C.R. Bertozzi, From mechanism to mouse: a tale of two bioorthogonal reactions. Acc. Chem. Res. 44(9), 666–676 (2011)

    Article  Google Scholar 

  27. C.R. Becer, R. Hoogenboom, U.S. Schubert, Click chemistry beyond metal-catalyzed cycloaddition. Angew. Chem. Int. Ed. Engl. 48(27), 4900–4908 (2009)

    Article  Google Scholar 

  28. J.C. Jewett, C.R. Bertozzi, Cu-free click cycloaddition reactions in chemical biology. Chem. Soc. Rev. 39(4), 1272–1279 (2010)

    Article  Google Scholar 

  29. J.M. Baskin, C.R. Bertozzi, Bioorthogonal click chemistry: covalent labeling in living systems. QSAR Comb. Sci. 26(11–12), 1211–1219 (2007)

    Article  Google Scholar 

  30. E.M. Sletten, C.R. Bertozzi, Bioorthogonal chemistry: fishing for selectivity in a sea of functionality. Angew. Chem. Int. Ed. Engl. 48(38), 6974–6998 (2009)

    Article  Google Scholar 

  31. J.M. Baskin, C.R. Bertozzi, Copper-free click chemistry: bioorthogonal reagents for tagging azides. Aldrichimica Acta 43(1), 15–23 (2010)

    Google Scholar 

  32. J.A. Codelli, J.M. Baskin, N.J. Agard, C.R. Bertozzi, Second-generation difluorinated cyclooctynes for copper-free click chemistry. J. Am. Chem. Soc. 130(34), 11486–11493 (2008)

    Article  Google Scholar 

  33. C.G. Gordon, J.L. Mackey, J.C. Jewett, E.M. Sletten, K.N. Houk, C.R. Bertozzi, Reactivity of biarylazacyclooctynones in copper-free click chemistry. J. Am. Chem. Soc. 134(22), 9199–9208 (2012)

    Article  Google Scholar 

  34. J. Dommerholt, O. Van Rooijen, A. Borrmann, C.F. Guerra, F.M. Bickelhaupt, F.L. Van Delft, Highly accelerated inverse electron-demand cycloaddition of electron-deficient azides with aliphatic cyclooctynes. Nat. Commun. 5, 5378 (2014)

    Article  Google Scholar 

  35. J. Dommerholt, F.P.J.T. Rutjes, F.L. van Delft, Strain-promoted 1,3-dipolar cycloaddition of cycloalkynes and organic azides. Top. Curr. Chem. 374(2), 16 (2016)

    Article  Google Scholar 

  36. V. Bouvet, M. Wuest, F. Wuest, Copper-free click chemistry with the short-lived positron emitter fluorine-18. Org. Biomol. Chem. 9(21), 7393–7399 (2011)

    Article  Google Scholar 

  37. D. Zeng, N.S. Lee, Y. Liu, D. Zhou, C.S. Dence, K.L. Wooley et al., 64Cu core-labeled nanoparticles with high specific activity via metal-free click chemistry. ACS Nano 6(6), 5209–5219 (2012)

    Article  Google Scholar 

  38. C. Pérez-Medina, D. Abdel-Atti, Y. Zhang, V.A. Longo, C.P. Irwin, T. Binderup et al., A modular labeling strategy for in vivo PET and near-infrared fluorescence imaging of nanoparticle tumor targeting. J. Nucl. Med. 55(10), 1706–1711 (2014)

    Article  Google Scholar 

  39. J. Schoch, M. Staudt, A. Samanta, M. Wiessler, A. Jäschke, Site-specific one-pot dual labeling of DNA by orthogonal cycloaddition chemistry. Bioconjug. Chem. 23(7), 1382–1386 (2012)

    Article  Google Scholar 

  40. M.R. Karver, R. Weissleder, S.A. Hilderbrand, Synthesis and evaluation of a series of 1,2,4,5-tetrazines for bioorthogonal conjugation. Bioconjug. Chem. 22(11), 2263–2270 (2011)

    Article  Google Scholar 

  41. K. Lang, L. Davis, S. Wallace, M. Mahesh, D.J. Cox, M.L. Blackman et al., Genetic encoding of bicyclononynes and trans-cyclooctenes for site-specific protein labeling in vitro and in live mammalian cells via rapid fluorogenic Diels-Alder reactions. J. Am. Chem. Soc. 134(25), 10317–10320 (2012)

    Article  Google Scholar 

  42. M.L. Blackman, M. Royzen, J.M. Fox, Tetrazine ligation: fast bioconjugation based on inverse-electron-demand Diels–Alder reactivity. J. Am. Chem. Soc. 130(41), 13518–13519 (2008)

    Article  Google Scholar 

  43. M.T. Taylor, M.L. Blackman, O. Dmitrenko, J.M. Fox, Design and synthesis of highly reactive dienophiles for the tetrazine-trans-cyclooctene ligation. J. Am. Chem. Soc. 133(25), 9646–9649 (2011)

    Article  Google Scholar 

  44. A.-C. Knall, C. Slugovc, Inverse electron demand Diels-Alder (iEDDA)-initiated conjugation: a (high) potential click chemistry scheme. Chem. Soc. Rev. 42(12), 5131–5142 (2013)

    Article  Google Scholar 

  45. J. Sauer, D.K. Heldmann, J. Hetzenegger, J. Krauthan, H. Sichert, J. Schuster, 1,2,4,5-Tetrazine: synthesis and reactivity in [4+2] cycloadditions. Euro. J. Org. Chem. 1998(12), 2885–2896 (1998)

    Article  Google Scholar 

  46. Z. Li, H. Cai, M. Hassink, M.L. Blackman, R.C.D. Brown, P.S. Conti et al., Tetrazine-trans-cyclooctene ligation for the rapid construction of 18F labeled probes. Chem. Commun. 46(42), 8043–8045 (2010)

    Article  Google Scholar 

  47. E.J. Keliher, T. Reiner, A. Turetsky, S.A. Hilderbrand, R. Weissleder, High-yielding, two-step 18F labeling strategy for 18F-PARP1 inhibitors. Chem. Med. Chem. 6(3), 424–427 (2011)

    Article  Google Scholar 

  48. T. Reiner, J. Lacy, E.J. Keliher, K.S. Yang, A. Ullal, R.H. Kohler et al., Imaging therapeutic PARP inhibition in vivo through bioorthogonally developed companion imaging agents. Neoplasia 14, 169–177 (2012)

    Article  Google Scholar 

  49. R. Selvaraj, S. Liu, M. Hassink, C. Huang, L. Yap, R. Park et al., Tetrazine-trans-cyclooctene ligation for the rapid construction of integrin αvβ3 targeted PET tracer based on a cyclic RGD peptide. Bioorg. Med. Chem. Lett. 21(17), 5011–5014 (2011)

    Article  Google Scholar 

  50. S. Liu, M. Hassink, R. Selvaraj, L.-P. Yap, R. Park, H. Wang et al., Efficient 18F labeling of cysteine-containing peptides and proteins using tetrazine–trans-cyclooctene ligation. Mol. Imaging 12, 121–128 (2013)

    Article  Google Scholar 

  51. Z. Wu, S. Liu, M. Hassink, I. Nair, R. Park, L. Li et al., Development and evaluation of 18F-TTCO-Cys40-Exendin-4: a PET probe for imaging transplanted islets. J. Nucl. Med. 54(2), 244–251 (2013)

    Article  Google Scholar 

  52. E.J. Keliher, T. Reiner, G.M. Thurber, R. Upadhyay, R. Weissleder, Efficient 18F-labeling of synthetic exendin-4 analogues for imaging beta cells. ChemistryOpen. 1(4), 177–183 (2012)

    Article  Google Scholar 

  53. J.C. Knight, B. Cornelissen, Bioorthogonal chemistry: implications for pretargeted nuclear (PET/SPECT) imaging and therapy. Am. J. Nucl. Med. Mol. Imaging 4(2), 96–113 (2014)

    Google Scholar 

  54. R. Rossin, M.S. Robillard, Pretargeted imaging using bioorthogonal chemistry in mice. Curr. Opin. Chem. Biol. 21, 161–169 (2014)

    Article  Google Scholar 

  55. R. Rossin, P. Renart Verkerk, S.M. van den Bosch, R.C.M. Vulders, I. Verel, J. Lub et al., In vivo chemistry for pretargeted tumor imaging in live mice. Angew. Chem. Int. Ed. Engl. 122(19), 3447–3450 (2010)

    Article  Google Scholar 

  56. B.M. Zeglis, K.K. Sevak, T. Reiner, P. Mohindra, S.D. Carlin, P. Zanzonico et al., A pretargeted PET imaging strategy based on bioorthogonal Diels–Alder click chemistry. J. Nucl. Med. 54(8), 1389–1396 (2013)

    Article  Google Scholar 

  57. S. Hou, J. Choi, M.A. Garcia, Y. Xing, K.-J. Chen, Y.-M. Chen et al., Pretargeted positron emission tomography imaging that employs supramolecular nanoparticles with in vivo bioorthogonal chemistry. ACS Nano 10(1), 1417–1424 (2016)

    Article  Google Scholar 

  58. H. Maeda, The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv. Enzyme Regul. 41(1), 189–207 (2001)

    Article  Google Scholar 

  59. H. Maeda, H. Nakamura, J. Fang, The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv. Drug Deliv. Rev. 65(1), 71–79 (2013)

    Article  Google Scholar 

  60. C. Heneweer, J.P. Holland, V. Divilov, S. Carlin, J.S. Lewis, Magnitude of enhanced permeability and retention effect in tumors with different phenotypes: 89Zr-albumin as a model system. J. Nucl. Med. 52(4), 625–633 (2011)

    Article  Google Scholar 

  61. O. Keinänen, E.M. Mäkilä, R. Lindgren, H. Virtanen, H. Liljenbäck, V. Oikonen et al., Pretargeted PET imaging of trans-cyclooctene-modified porous silicon nanoparticles. ACS Omega 2(1), 62–69 (2017)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, CR-UK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK

    James C. Knight & Bart Cornelissen

Authors
  1. James C. Knight
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bart Cornelissen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to James C. Knight or Bart Cornelissen .

Editor information

Editors and Affiliations

  1. Department of Nuclear Medicine, Seoul National University, Seoul, Korea (Republic of)

    Dong Soo Lee

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Knight, J.C., Cornelissen, B. (2018). Preservation of Ligand Functionality by Click Chemistry. In: Lee, D. (eds) Radionanomedicine. Biological and Medical Physics, Biomedical Engineering. Springer, Cham. https://doi.org/10.1007/978-3-319-67720-0_13

Download citation

Publish with us

Policies and ethics

Search

Navigation