Alternative chelator for ⁸⁹Zr radiopharmaceuticals: radiolabeling and evaluation of 3,4,3-(LI-1,2-HOPO)

J Med Chem. 2014 Jun 12;57(11):4849-60. doi: 10.1021/jm500389b. Epub 2014 May 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Chelating Agents / chemistry*
  • Chelating Agents / pharmacokinetics
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacokinetics
  • Drug Stability
  • Female
  • Isotope Labeling
  • Mice
  • Mice, Nude
  • Positron-Emission Tomography
  • Pyridones / chemistry*
  • Pyridones / pharmacokinetics
  • Radioisotopes
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / pharmacokinetics
  • Spermine / analogs & derivatives*
  • Spermine / chemistry
  • Spermine / pharmacokinetics
  • Tissue Distribution
  • Zirconium*


  • 1,14-bis(1-hydroxy-2-pyridon-6-oyl)-5,10-bis(3-hydroxy-1-methyl-2-pyridon-4-oyl)-1,5,10,14-tetraazatetradecane
  • Chelating Agents
  • Coordination Complexes
  • Pyridones
  • Radioisotopes
  • Radiopharmaceuticals
  • Spermine
  • Zirconium