title: Alternative chelator for ⁸⁹Zr radiopharmaceuticals: radiolabeling and evaluation of 3,4,3-(LI-1,2-HOPO).
abstract: 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.
authors.affiliation: Department of Radiology and the Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Deri
authors.forename: Shashikanth
authors.initials: S
authors.lastname: Ponnala
authors.forename: Brian M
authors.initials: BM
authors.lastname: Zeglis
authors.forename: Gabor
authors.initials: G
authors.lastname: Pohl
authors.forename: J J
authors.initials: JJ
authors.lastname: Dannenberg
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Francesconi
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D056831:Coordination Complexes / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D005260:Female; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D011728:Pyridones / Q000737:chemistry* / Q000493:pharmacokinetics; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics; D013096:Spermine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015040:Zirconium
chemical_list: C465462:1,14-bis(1-hydroxy-2-pyridon-6-oyl)-5,10-bis(3-hydroxy-1-methyl-2-pyridon-4-oyl)-1,5,10,14-tetraazatetradecane; D002614:Chelating Agents; D056831:Coordination Complexes; D011728:Pyridones; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D013096:Spermine; D015040:Zirconium