title: Standardized methods for the production of high specific-activity zirconium-89.
abstract: Zirconium-89 is an attractive metallo-radionuclide for use in immuno-PET due to favorable decay characteristics. Standardized methods for the routine production and isolation of high-purity and high-specific-activity (89)Zr using a small cyclotron are reported. Optimized cyclotron conditions reveal high average yields of 1.52+/-0.11 mCi/muA.h at a proton beam energy of 15 MeV and current of 15 muA using a solid, commercially available (89)Y-foil target (0.1 mm, 100% natural abundance). (89)Zr was isolated in high radionuclidic and radiochemical purity (>99.99%) as [(89)Zr]Zr-oxalate by using a solid-phase hydroxamate resin with >99.5% recovery of the radioactivity. The effective specific-activity of (89)Zr was found to be in the range 5.28-13.43 mCi/microg (470-1195 Ci/mmol) of zirconium. New methods for the facile production of [(89)Zr]Zr-chloride are reported. Radiolabeling studies using the trihydroxamate ligand desferrioxamine B (DFO) gave 100% radiochemical yields in <15 min at room temperature, and in vitro stability measurements confirmed that [(89)Zr]Zr-DFO is stable with respect to ligand dissociation in human serum for >7 days. Small-animal positron emission tomography (PET) imaging studies have demonstrated that free (89)Zr(IV) ions administered as [(89)Zr]Zr-chloride accumulate in the liver, whilst [(89)Zr]Zr-DFO is excreted rapidly via the kidneys within <20 min. These results have important implication for the analysis of immuno-PET imaging of (89)Zr-labeled monoclonal antibodies. The detailed methods described can be easily translated to other radiochemistry facilities and will facilitate the use of (89)Zr in both basic science and clinical investigations.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY 10065, USA. hollanj3@mskcc.org
authors.forename: Jason P
authors.initials: JP
authors.lastname: Holland
authors.forename: Yiauchung
authors.initials: Y
authors.lastname: Sheh
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
mesh_terms: D000818:Animals; D019985:Benchmarking; D002614:Chelating Agents / Q000737:chemistry; D017357:Cyclotrons; D003676:Deferoxamine / Q000737:chemistry; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D008024:Ligands; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D011868:Radioisotopes; D015203:Reproducibility of Results; D015040:Zirconium / Q000737:chemistry*
chemical_list: D002614:Chelating Agents; D006877:Hydroxamic Acids; D008024:Ligands; D011868:Radioisotopes; D015040:Zirconium; D003676:Deferoxamine