4.7 Article

Click chemistry: a transformative technology in nuclear medicine

Journal

NATURE PROTOCOLS
Volume 18, Issue 6, Pages 1659-1668

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41596-023-00825-8

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The 2022 Nobel Prize in Chemistry was awarded to Professors K. Barry Sharpless, Morten Meldal and Carolyn Bertozzi for their pioneering roles in the advent of click chemistry. The development of click reactions has revolutionized chemical and biological science, providing unprecedented methods for manipulating living systems. Click chemistry has had a significant impact on radiopharmaceutical chemistry, improving efficiency and potentially advancing nuclear medicine.
The 2022 Nobel Prize in Chemistry was awarded to Professors K. Barry Sharpless, Morten Meldal and Carolyn Bertozzi for their pioneering roles in the advent of click chemistry. Sharpless and Meldal worked to develop the canonical click reaction-the copper-catalyzed azide-alkyne cycloaddition-while Bertozzi opened new frontiers with the creation of the bioorthogonal strain-promoted azide-alkyne cycloaddition. These two reactions have revolutionized chemical and biological science by facilitating selective, high yielding, rapid and clean ligations and by providing unprecedented ways to manipulate living systems. Click chemistry has affected every aspect of chemistry and chemical biology, but few disciplines have been impacted as much as radiopharmaceutical chemistry. The importance of speed and selectivity in radiochemistry make it an almost tailor-made application of click chemistry. In this Perspective, we discuss the ways in which the copper-catalyzed azide-alkyne cycloaddition, the strain-promoted azide-alkyne cycloaddition and a handful of 'next-generation' click reactions have transformed radiopharmaceutical chemistry, both as tools for more efficient radiosyntheses and as linchpins of technologies that have the potential to improve nuclear medicine. This Perspective explains how click chemistry-specifically, the copper-catalyzed azide-alkyne cycloaddition, the strain-promoted azide-alkyne cycloaddition and the inverse electron-demand Diels-Alder reaction-has revolutionized radiopharmaceutical chemistry.

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