Standardized methods for the production of high specific-activity zirconium-89.
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.
Holland
Jason P
JP
Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY 10065, USA. hollanj3@mskcc.org
Sheh
Yiauchung
Y
Lewis
Jason S
JS
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*
D002614:Chelating Agents; D006877:Hydroxamic Acids; D008024:Ligands; D011868:Radioisotopes; D015040:Zirconium; D003676:Deferoxamine