Chapter 14
Bioorthogonal Reaction for Fluorine-18
Labeling
Dong Wook Kim
Abstract Specific molecular imaging probes including radiopharmaceuticals
labeled with positron-emitters, such as fluorine-18 (
18 F, t 1/2 = 109.8 min), need to
expand their applications of positron emission tomography (PET) molecular imaging study. In recent years, bioorthogonal chemistry such as inverse electron-demand
Diels-Alder cycloaddition reactions and strain-promoted alkyne azide cycloaddition
(SPAAC) has been regarded as alternative bioorthogonal ligation reactions of
bioactive molecules with radiolabeled building blocks. In this chapter, I will introduce an overview of this emerging synthetic strategies based on the catalyst-free
SPAAC conjugation reaction and Diels-Alder cycloaddition reactions using tetrazine/trans-cyclooctene (TCO) derivatives under physiologically-friendly reaction
conditions. I will also introduce that the pretargeting method by the SPAAC reaction
for tracking mesoporous silica nanoparticles (MSNs) in in vivo system. This
bioorthogonal SPAAC-based pretargeting protocol allow
18 F with a short half-life to
be used for labeling of the MSNs to obtain their tracking PET images.
14.1 Cu-Catalyzed Click Reaction
Copper (I) catalyzed azide alkyne [3+2] cycloaddition (CuAAC), which referred to
as “click chemistry”, has received much attention in biomedical area because this
click chemistry provided the facile conjugation protocol of biomolecules with a
range of functional groups as well as radiolabeling method for the synthesis of
molecular imaging probes [1–5]. On the other hand, this CuAAC reaction-based
click bioconjugation reaction had limitations in synthetic operation as follows; the
frequent undesired interaction of Cu(I) catalyst with biomolecules, such as peptide
and antibody, that make this CuAAC reaction blocked or reduce the reaction rate.
D. W. Kim (&)
Department of Chemistry, Inha University, 100 Inha-ro, Nam-gu,
Incheon 402-751, Korea
e-mail: kimdw@inha.ac.kr
© 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_14
263
Bioorthogonal Reaction for Fluorine-18
Labeling
Dong Wook Kim
Abstract Specific molecular imaging probes including radiopharmaceuticals
labeled with positron-emitters, such as fluorine-18 (
18 F, t 1/2 = 109.8 min), need to
expand their applications of positron emission tomography (PET) molecular imaging study. In recent years, bioorthogonal chemistry such as inverse electron-demand
Diels-Alder cycloaddition reactions and strain-promoted alkyne azide cycloaddition
(SPAAC) has been regarded as alternative bioorthogonal ligation reactions of
bioactive molecules with radiolabeled building blocks. In this chapter, I will introduce an overview of this emerging synthetic strategies based on the catalyst-free
SPAAC conjugation reaction and Diels-Alder cycloaddition reactions using tetrazine/trans-cyclooctene (TCO) derivatives under physiologically-friendly reaction
conditions. I will also introduce that the pretargeting method by the SPAAC reaction
for tracking mesoporous silica nanoparticles (MSNs) in in vivo system. This
bioorthogonal SPAAC-based pretargeting protocol allow
18 F with a short half-life to
be used for labeling of the MSNs to obtain their tracking PET images.
14.1 Cu-Catalyzed Click Reaction
Copper (I) catalyzed azide alkyne [3+2] cycloaddition (CuAAC), which referred to
as “click chemistry”, has received much attention in biomedical area because this
click chemistry provided the facile conjugation protocol of biomolecules with a
range of functional groups as well as radiolabeling method for the synthesis of
molecular imaging probes [1–5]. On the other hand, this CuAAC reaction-based
click bioconjugation reaction had limitations in synthetic operation as follows; the
frequent undesired interaction of Cu(I) catalyst with biomolecules, such as peptide
and antibody, that make this CuAAC reaction blocked or reduce the reaction rate.
D. W. Kim (&)
Department of Chemistry, Inha University, 100 Inha-ro, Nam-gu,
Incheon 402-751, Korea
e-mail: kimdw@inha.ac.kr
© 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_14
263