Researchers at the NCI Radiation Oncology Branch and NIH CIT Center for Molecular Modeling developed a tetrahydroxamate chelation technology that provides a more-stable Zr-89 complex as an immuno-PET cancer imaging agent. In either the linear or the macrocyclic form, the tetrahydroxamate complexes exhibit greater stability as chelating agents compared to Zr-89 complexed to the siderophore desferrioxamine B (DFB), a trihydroxamate, which represents the current state of the art chemistry and the agent currently in clinical use.
In the Zr-89-DFB imaging agents, Zr-89 dissociates from the chelate, resulting in an increasing radioisotope accumulation in the bone 2-3 days after injection. In vitro studies demonstrate the tetrahydroxamate-chelated Zr-89 remained kinetically inert for seven or more days, thereby reducing the amount of Zr-89 that is released compared to the complex containing DFB.