Abstract
Specific molecular imaging probes including radiopharmaceuticals labeled with positron-emitters, such as fluorine-18 (18F, t1/2 = 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 18F with a short half-life to be used for labeling of the MSNs to obtain their tracking PET images.
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