Chapter 13
Preservation of Ligand Functionality
by Click Chemistry
James C. Knight and Bart Cornelissen
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.
J. C. Knight (&) Á B. Cornelissen (&)
Department of Oncology, CR-UK/MRC Oxford Institute for Radiation Oncology,
University of Oxford, Oxford, UK
e-mail: james.knight@oncology.ox.ac.uk
B. Cornelissen
e-mail: bart.cornelissen@oncology.ox.ac.uk
© Springer International Publishing AG, part of Springer Nature 2018
D. S. Lee (ed.), Radionanomedicine, Biological and Medical Physics,
Biomedical Engineering, https://doi.org/10.1007/978-3-319-67720-0_13
251
Preservation of Ligand Functionality
by Click Chemistry
James C. Knight and Bart Cornelissen
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.
J. C. Knight (&) Á B. Cornelissen (&)
Department of Oncology, CR-UK/MRC Oxford Institute for Radiation Oncology,
University of Oxford, Oxford, UK
e-mail: james.knight@oncology.ox.ac.uk
B. Cornelissen
e-mail: bart.cornelissen@oncology.ox.ac.uk
© Springer International Publishing AG, part of Springer Nature 2018
D. S. Lee (ed.), Radionanomedicine, Biological and Medical Physics,
Biomedical Engineering, https://doi.org/10.1007/978-3-319-67720-0_13
251