Review highlights newest advances in 89Zr chelation chemistry and development of DFO alternatives

A review published in the March issue of Molecules1 compiles the latest developments in the search for chelators that improve the bioconjugation of 89Zr for clinical use.

The authors highlight that the introduction of 89Zr more than thirty years ago reignited the interest in the rapidly expanding clinical possibilities of immuno-PET. This field has grown even more over the last decade thanks to the standardized production of 89Zr, its long half-life (78.2 hours), favorable decay characteristics for PET imaging, and successful application in various clinical and preclinical studies.

Hoewever, the preparation of 89Zr-labeled antibodies for clinical application in tumor imaging (89Zr-immuno-PET) strongly depends on adequate chelators to enable stable bioconjugation. Although there have been enormous advances in this area, and numerous siderophore-inspired ligands (containing hydroxamate, hydroxyisopthalamide, terepthalamide and hydroxypiridinoate coordinating units) have been reported to effectively chelate 89Zr, so far only desferrioxamine B (DFO) and 3-hydroxy-4-pyridinone (HOPO) derivatives have proven effective as 89Zr chelators when incorporated into an antibody-based radiopharmaceutical. Still, there is currently growing interest in tetraazamacrocycles as 89Zr chelators, owing to the recent revelation that this ligand class is able to form ultra-stable 89Zr complexes.

89Zr-immuno-PET will changing the PET landscape
Therefore, while DFO is a prevalent and commercially available alternative, research has continuously focused on the development of new ligands for this radiometal. New insights and exciting breakthroughs in 89Zr-immuno-PET radiopharmaceutical design are expected in the next fiew years. This may change the landscape of how precision medicine strategies are implemented in the clinical practice.


1 Bhat NB, Pandya DN, Wadas TJ (2018). Recent advances in Zirconium-89 chelator development. Molecules 23(3): 638.