Light-Activated Protein Conjugation and 89Zr-Radiolabelling with Water-Soluble Desferrioxamine Derivatives |
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Authors: | Dr Amaury Guillou Dr Daniel F Earley Prof Dr Jason P Holland |
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Institution: | University of Zurich, Department of Chemistry, Winterthurerstrasse 190, Zurich, 8057 Switzerland |
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Abstract: | Protein-conjugates are vital tools in biomedical research, drug discovery and imaging science. For example, functionalised monoclonal antibodies (mAbs) coupled to the desferrioxamine B (DFO) chelate and radiolabelled with 89Zr4+ ions are used as radiopharmaceuticals for diagnostic positron emission tomography (PET). In this context, protein functionalisation requires the formation of a covalent bond that must be achieved without compromising the biological properties of the mAb. Photochemistry offers new synthetic routes toward protein conjugates like 89Zr-mAbs but to harness the potential of light-induced conjugation reactions new photoactivatable reagents are required. Herein, we introduce two photoactivatable DFO-derivatives functionalised with an aryl azide (ArN3) for use in light-activated conjugation and radiosynthesis of 89Zr-mAbs. Incorporation of a tris-polyethylene glycol (PEG)3 linker between DFO and the ArN3 group furnished water-soluble chelates that were used in the one-pot, photoradiosynthesis of different 89Zr-radiolabelled protein conjugates with radiochemical yields up to 72.9±1.9 %. Notably, the DFO-PEG3 chelates can be readily synthesised in accordance with Good Laboratory Practice (GLP), which will facilitate clinical trials with photoradiolabelled 89Zr-mAbs. |
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Keywords: | antibody conjugates photochemistry positron emission tomography radiochemistry zirconium-89 |
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