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The inverse electron demand Diels–Alder click reaction in radiochemistry
Author(s) -
Reiner Thomas,
Zeglis Brian M.
Publication year - 2014
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3149
Subject(s) - bioorthogonal chemistry , chemistry , click chemistry , combinatorial chemistry , in vivo , cycloaddition , nanotechnology , organic chemistry , catalysis , microbiology and biotechnology , materials science , biology
The inverse electron‐demand Diels‐Alder (IEDDA) cycloaddition between 1,2,4,5‐tetrazines and strained alkene dienophiles is an emergent variety of catalyst‐free ‘click’ chemistry that has the potential to have a transformational impact on the synthesis and development of radiopharmaceuticals. The ligation is selective, rapid, high‐yielding, clean, and bioorthogonal and, since its advent in 2008, has been employed in a wide variety of chemical settings. In radiochemistry, the reaction has proven particularly useful with 18 F and has already been utilized to create a number of 18 F‐labeled agents, including the PARP1‐targeting small molecule 18 F‐AZD2281, the α v β 3 integrin‐targeting peptide 18 F‐RGD, and the GLP‐1‐targeting peptide 18 F‐exendin. The inherent flexibility of the ligation has also been applied to the construction of radiometal‐based probes, specifically the development of a modular strategy for the synthesis of radioimmunoconjugates that effectively eliminates variability in the construction of these agents. Further, the exceptional speed and biorthogonality of the reaction have made it especially promising in the realm of in vivo pretargeted imaging and therapy, and pretargeted imaging strategies based on the isotopes 111 In, 18 F, and 64 Cu have already proven capable of producing images with high tumor contrast and low levels of uptake in background, nontarget organs. Ultimately, the characteristics of inverse electron‐demand Diels–Alder click chemistry make it almost uniquely well‐suited for radiochemistry, and although the field is young, this ligation has the potential to make a tremendous impact on the synthesis, development, and study of novel radiopharmaceuticals. Copyright © 2013 John Wiley & Sons, Ltd.