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 (89)Zr(4+); however, accumulation of (89)Zr in the bones of mice suggests that (89)Zr(4+) is released from DFO in vivo. An improved chelator for (89)Zr(4+) could eliminate the release of osteophilic (89)Zr(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 (89)Zr-HOPO matched or surpassed that of (89)Zr-DFO in every experiment. In healthy mice, (89)Zr-HOPO cleared the body rapidly with no signs of demetalation. Ultimately, HOPO has the potential to replace DFO as the chelator of choice for (89)Zr-based PET imaging agents.