Light‐Activated Protein Conjugation and ⁸⁹Zr‐Radiolabelling with Water‐Soluble Desferrioxamine Derivatives

Abstract

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 89 Zr 4+ 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 89 Zr‐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 (ArN 3 ) for use in light‐activated conjugation and radiosynthesis of 89 Zr‐mAbs. Incorporation of a tris‐polyethylene glycol (PEG) 3 linker between DFO and the ArN 3 group furnished water‐soluble chelates that were used in the one‐pot, photoradiosynthesis of different 89 Zr‐radiolabelled protein conjugates with radiochemical yields up to 72.9±1.9 %. Notably, the DFO‐PEG 3 chelates can be readily synthesised in accordance with Good Laboratory Practice (GLP), which will facilitate clinical trials with photoradiolabelled 89 Zr‐mAbs.