Copper-free click - A promising tool for pre-targeted PET imaging

Comprehensive Cancer Imaging Centre, Department of Surgery & Cancer, Hammersmith Campus, Imperial College, London, United Kingdom.
Chemical Communications (Impact Factor: 6.83). 12/2011; 48(7):991-3. DOI: 10.1039/c1cc16220a
Source: PubMed


The copper-free click (CFC) reaction has been evaluated for its potential application to in vivo pre-targeting for PET imaging. A promising biodistribution profile is demonstrated when employing [(18)F]2-fluoroethylazide ([(18)F]1) and optimisation of the CFC reaction with a series of cyclooctynes shows that reactions proceed efficiently with tantalizing opportunities for application-specific tuning.

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Available from: Laurence Carroll, Oct 09, 2015
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    • "However, the need of cytotoxic copper during CuAAC has led to the necessity of alternative fast and copper-free click reaction strategies for radiofluorination and additionally enabling pretargeting approaches in living systems. Those so-called strain-promoted click reactions can be carried out between cyclooctyne derivatives and azides (strain-promoted azide-alkyne cycloaddition, SPAAC) [7] [8] [9] [10] [11] [12] [13] or tetrazines (tetrazine-trans-cyclooctyne (TTCO) ligation) [14] [15] [16] [17] as well as between norbornene derivatives and tetrazines [18]. Especially , the TTCO ligation showed promising reaction rates, which makes this click reaction concept very suitable for 18 Flabeling and also for in vivo application in living systems. "
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    ABSTRACT: Due to expanding applications of positron emission tomography (PET) there is a demand for developing new techniques to introduce fluorine-18 (t 1/2 = 109.8 min). Considering that most novel PET tracers are sensitive biomolecules and that direct introduction of fluorine-18 often needs harsh conditions, the insertion of (18)F in those molecules poses an exceeding challenge. Two major challenges during (18)F-labeling are a regioselective introduction and a fast and high yielding way under mild conditions. Furthermore, attention has to be paid to functionalities, which are usually present in complex structures of the target molecule. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) and several copper-free click reactions represent such methods for radiolabeling of sensitive molecules under the above-mentioned criteria. This minireview will provide a quick overview about the development of novel (18)F-labeled prosthetic groups for click cycloadditions and will summarize recent trends in copper-catalyzed and copper-free click (18)F-cycloadditions.
    BioMed Research International 05/2014; 2014(13):361329. DOI:10.1155/2014/361329 · 2.71 Impact Factor
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    • "Given their apparent high selectivity and promising rates of reaction in some cases, it is not surprising that SPAAC reactions have been considered as candidates to facilitate a pretargeting approach [130] [133] [134]. "
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    ABSTRACT: Due to their rapid and highly selective nature, bioorthogonal chemistry reactions are attracting a significant amount of recent interest in the radiopharmaceutical community. Over the last few years, reactions of this type have found tremendous utility in the construction of new radiopharmaceuticals and as a method of bioconjugation. Furthermore, reports are beginning to emerge in which these reactions are also being applied in vivo to facilitate a novel pretargeting strategy for the imaging and therapy of cancer. The successful implementation of such an approach could lead to dramatic improvements in image quality, therapeutic index, and reduced radiation dose to non-target organs and tissues. This review will focus on the potential of various bioorthogonal chemistry reactions to be used successfully in such an approach.
    American Journal of Nuclear Medicine and Molecular Imaging 04/2014; 4(2):96-113. · 3.25 Impact Factor
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    • "Copper is an essential trace element for all living organisms participating in various biological functions (Evans et al., 2012; Tisato et al., 2010) such as development, immune function, neovascularization processes, maintenance of neuroendocrine function and iron metabolism (O'Dell & Sunde, 1997). After iron and zinc, copper is the most abundant mineral in human body. "
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