Tuning Tetrazole Photochemistry for Protein Ligation and Molecular Imaging

Photochemistry provides a wide range of alternative reagents that hold potential for use in bimolecular functionalisation proteins. Here, we report the synthesis and characterisation metal ion binding chelates derivatised with disubstituted tetrazoles photoradiochemical labelling monoclonal antibodies (mAbs). The photophysical properties featuring extended aromatic systems auxochromic substituents to tune excitation toward longer wavelengths (365 395 nm) were studied. Two photoactivatable based on desferrioxamine B (DFO) aza-macrocycle NODAGA functionalised tetrazole developed protein 89Zr, 64Cu 68Ga radionuclides. DFO-tetrazole (1) was assessed by direct conjugation formulated trastuzumab subsequent radiolabelling 89Zr. Radiochemical studies cellular-based assays demonstrated radiotracer remained stable vitro retained high immunoreactivity. Positron emission tomography (PET) imaging biodistribution used measure tumour specific uptake pharmacokinetic profile mice bearing SK-OV-3 xenografts. Experiments demonstrate tetrazole-based photochemistry is viable approach light-induced PET radiotracers.