Standardized methods for the production of high specific-activity zirconium-89

Zirconium-89 is an attractive metallo-radionuclide for use in immuno-PET clue to favorable decay characteristics. Standardized methods for the routine production and isolation of high-purity and high-specific-activity Zr-89 using a small cyclotron are reported. Optimized cyclotron conditions reveal high average yields of 1.52+/-0.11 mCi/mu A.h at a proton beam energy of 15 MeV and current of 15 mu A using a solid, commercially available Y-89-foil target (0.1 mm, 100% natural abundance). Zr-89 was isolated in high radionuclidic and radiochemical purity (>99.99%) as [Zr-89]Zr-oxalate by using a solid-phase hydroxamate resin with >99.5% recovery of the radioactivity. The effective specific-activity of Zr-89 was found to be in the range 5.28-13.43 mCi/mu g (470-1195 Ci/mmol) of zirconium. New methods for the facile production of [Zr-89]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 [Zr-89]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 Zr-89(IV) ions administered as [Zr-89]Zr-chloride accumulate in the liver, whilst [Zr-89]Zr-DFO is excreted rapidly via the kidneys within <20 min. These results have important implication for the analysis of immuno-PET imaging of Zr-89-labeled monoclonal antibodies. The detailed methods described can be easily translated to other radiochemistry facilities and will facilitate the use of Zr-89 in both basic science and clinical investigations. (C) 2009 Elsevier Inc. All rights reserved.