Recent Advances in Bioorthogonal Click Chemistry for Enhanced PET and SPECT Radiochemistry

Abstract

Due to their high reaction rate and reliable selectivity, bioorthogonal click reactions have been extensively investigated in numerous research fields, such as nanotechnology, drug delivery, molecular imaging, and targeted therapy. Previous reviews on bioorthogonal click chemistry for radiochemistry mainly focus on 18F-labeling protocols employed to produce radiotracers and radiopharmaceuticals. In fact, besides fluorine-18, other radionuclides such as gallium-68, iodine-125, and technetium-99m are also used in the field of bioorthogonal click chemistry. Herein, to provide a more comprehensive perspective, we provide a summary of recent advances in radiotracers prepared using bioorthogonal click reactions, including small molecules, peptides, proteins, antibodies, and nucleic acids as well as nanoparticles based on these radionuclides. The combination of pretargeting with imaging modalities or nanoparticles, as well as the clinical translations study, are also discussed to illustrate the effects and potential of bioorthogonal click chemistry for radiopharmaceuticals.

Click Chemistry and Radiochemistry: An Update

“…In response to feedback on the original piece, we have altered course a bit in the organization of this review by pivoting to sections based on the type of click reaction rather than the application of the technology within radiopharmaceutical chemistry. Of course, we are not the only ones to write about the contribution of click chemistry to the radiopharmaceutical sciences, so we would be remiss if we did not direct the reader to a handful of reviews that can provide differing yet no less valuable vantage points. − It is also important to note that a variety of other coupling reactions have been employed in radiopharmaceutical chemistry but will not be discussed here because they do not meet the definitional criteria for “click chemistry” as originally laid out by Kolb et al For example, the Michael addition between maleimides and thiols is selective, but the thioether product is notoriously unstable in vivo ; similarly, N -hydroxysuccinimidyl esters react efficiently with primary amines, but the former are prone to hydrolysis in water. In the end, it is our hope that this Review will provide a comprehensive portrait of the current state of this exciting discipline, illustrate how the radiopharmaceutical applications of click chemistry have grown more sophisticated in recent years, and inspire innovative new work at the junction of these two fields.…”

Click-derived multifunctional metal complexes for diverse applications

“…While there are difficulties with the selective and reliable making of molecular connections, the newly emerged fields of Click and bio-orthogonal chemistry have paved the way for the development of new chemical reactions along with their accurate mechanistic insights. 21 The initial Click reactions are highly admired in the history of organic synthesis and reactions include the following: cycloaddition, 22,23 conjugate addition, 24 opening of strained rings, 25 acylation/sulfonylation, 26 a-effect nucleophilic aldehyde capture, etc. The first fundamental breakthrough with the Click chemistry concept happened with the copper-mediated azidealkyne cycloaddition reaction that was further associated with other biocompatible predecessors and made this a hot and more significant field of research.…”

“…27 In pharmaceutical and polymer sciences research, various types of Click chemistry have been employed for drug delivery applications. 18,21,28 In diagnostic and theranostic research, many luminescent probes have been reported to sense a variety of biological, chemical and environmental analytes but there are still challenges with tuning the luminescence properties of these probes. 29,30 Similarly, the roles of thiazetidines, quinolines and fused imidazoquinolines towards anti-cancer and anti-microbial properties were explored through computational methods, 31,32 but there are limitations in synthesizing these structures; Click chemistry can be employed to overcome these drawbacks.…”

“…While there are difficulties with the selective and reliable making of molecular connections, the newly emerged fields of Click and bio-orthogonal chemistry have paved the way for the development of new chemical reactions along with their accurate mechanistic insights. 21…”

A Brief Guide to Preparing a Peptide–Drug Conjugate

“…Targeted therapy represents an emerging paradigm for the current biomedical research, as selective and precise delivery of drugs to diseased tissues can be a good strategy to improve the therapeutic efficiency of the drug/probe, to overcome drug resistance, to reduce the off-target effects and to early detect several diseased states. [1,2] Recently, peptide-drug conjugates (PDCs) have emerged as interesting tools for cancer-targeted therapy and some representatives of this class are already in clinical trials. [3,4] In particular, two PDCs are currently on the market: melfuflen for the treatment of multiple myeloma and lutathera for the therapy of gastroenteropancreatic neuroendocrine tumours.…”