Bioorthogonal click chemistry for fluorine-18 labeling protocols under physiologically friendly reaction condition

• Developments of novel specific radiopharmaceuticals are necessary for PET study.
• Strain-promoted alkyne azide cycloaddition (SPAAC) does not need any catalysts.
• SPAAC reaction regards as an alternative bioorthogonal ligation for F-18 labeling.
• We report synthetic strategies for the synthesis of 18F-labeled peptides via SPAAC.
• We report MSNs pretargeting for PET imaging via SPAAC labeling in living specimen.

To expand the applications of positron emission tomography (PET), novel specific radiopharmaceuticals using positron-emitters, such as fluorine-18 (F-18, t1/2 = 109.8 min), will be needed. Recently, strain-promoted alkyne azide cycloaddition (SPAAC) has been considered as an alternative bioorthogonal conjugation reaction between bioactive molecules and radiolabeled building blocks for the synthesis of novel radiopharmaceuticals. This mini-review provides a rapid overview of the emerging synthetic strategies based on the copper-free SPAAC conjugation reaction under physiologically-friendly reaction conditions for the high-throughput synthesis of 18F-labeled peptide tracers. Furthermore, an efficient mesoporous silica nanoparticles (MSNs) pretargeting for PET imaging were also introduced through the in situ bioorthogonal SPAAC labeling reaction by forming 18F-labeled MSNs at the tumor site in a living specimen.

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