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

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 Zr⁴⁺ 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 (ArN₃ ) 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 ArN₃ 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-PEG₃ chelates can be readily synthesised in accordance with Good Laboratory Practice (GLP), which will facilitate clinical trials with photoradiolabelled ⁸⁹ Zr-mAbs.