Alternative Chelator for 89Zr Radiopharmaceuticals: Radiolabeling and Evaluation of 3,4,3-(LI-1,2-HOPO)

Zirconium-89 is an effective radionuclide for antibody-based positron emission tomography (PET) imaging because its physical half-life (78.41 h) matches the biological half-life of IgG antibodies. Desferrioxamine (DFO) is currently the preferred chelator for Zr-89(4+); however, accumulation of Zr-89 in the bones of mice suggests that Zr-89(4+) is released from DFO in vivo. An improved chelator for Zr-89(4+) could eliminate the release of osteophilic Zr-89(4+) and lead to a safer PET tracer with reduced background radiation dose. Herein, we present an octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO) as a potentially superior alternative to DFO. The HOPO ligand formed a 1:1 Zr-HOPO complex that was evaluated experimentally and theoretically. The stability of Zr-89-HOPO matched or surpassed that of Zr-89-DFO in every experiment. In healthy mice, Zr-89-HOPO cleared the body rapidly with no signs of demetalation. Ultimately, HOPO has the potential to replace DFO as the chelator of choice for Zr-89-based PET imaging agents.