Hydrazinonicotinic acid (HYNIC) – Coordination chemistry and applications in radiopharmaceutical chemistry

HYNIC (hydrazinonicotinamide) is an efficient bifunctional chelator for Tc-99m used for labelling biomolecules for molecular imaging. Developments and enhancements to improve its efficacy and versatility, including applications beyond Tc-99m labelling, include designs to allow site specificity, availability of amino acid building blocks, improved protecting groups, and a varied choice of co-ligands. In this review, these enhancements are summarised, along with an assessment of the opportunities afforded and problems posed by the use of HYNIC, a discussion of its coordination mode, and the prospects for improving its use and overcoming some of the limitations. There is now an opportunity to exploit the excellent labelling kinetics associated with the tricine-HYNIC system with better co-ligand design to enable both efficient production of labelled proteins and peptides and better specific activity and in vivo properties. In summary, HYNIC represents a well-established way to exploit the highly reactive hydrazine group, to generate bioconjugate chemistry with a degree of bioorthogonality offering the possibility for highly efficient and site specific modification of biomolecules for imaging.