Standardized methods for the production of high specific-activity zirconium-89 Journal Article
| Authors: | Holland, J. P.; Sheh, Y.; Lewis, J. S. |
| Article 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 <sup>89</sup>Zr using a small cyclotron are reported. Optimized cyclotron conditions reveal high average yields of 1.52±0.11 mCi/μA·h at a proton beam energy of 15 MeV and current of 15 μA using a solid, commercially available <sup>89</sup>Y-foil target (0.1 mm, 100% natural abundance). <sup>89</sup>Zr was isolated in high radionuclidic and radiochemical purity (>99.99%) as [<sup>89</sup>Zr]Zr-oxalate by using a solid-phase hydroxamate resin with >99.5% recovery of the radioactivity. The effective specific-activity of <sup>89</sup>Zr was found to be in the range 5.28-13.43 mCi/μg (470-1195 Ci/mmol) of zirconium. New methods for the facile production of [<sup>89</sup>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 [<sup>89</sup>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 <sup>89</sup>Zr(IV) ions administered as [<sup>89</sup>Zr]Zr-chloride accumulate in the liver, whilst [<sup>89</sup>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 <sup>89</sup>Zr-labeled monoclonal antibodies. The detailed methods described can be easily translated to other radiochemistry facilities and will facilitate the use of <sup>89</sup>Zr in both basic science and clinical investigations. © 2009 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; nonhuman; positron emission tomography; radiopharmaceuticals; reproducibility of results; mouse; animals; mice; image analysis; drug specificity; drug synthesis; time; monoclonal antibody; standardization; isotope labeling; positron-emission tomography; hydroxamic acids; ligands; benchmarking; kidney clearance; drug purity; radioisotope; radioisotopes; radiation energy; yttrium; zirconium; radioisotope decay; cyclotron targetry; desferrioxamine; hydroxamates; zirconium-89; deferoxamine mesylate; hydroxamic acid; resin; zirconium 89; zirconium derivative; zirconium tetrachloride; bioaccumulation; cyclotron; drug excretion; drug isolation; drug stability; proton radiation; room temperature; chelating agents; cyclotrons; deferoxamine |
| Journal Title: | Nuclear Medicine and Biology |
| Volume: | 36 |
| Issue: | 7 |
| ISSN: | 0969-8051 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2009-10-01 |
| Start Page: | 729 |
| End Page: | 739 |
| Language: | English |
| DOI: | 10.1016/j.nucmedbio.2009.05.007 |
| PUBMED: | 19720285 |
| PROVIDER: | scopus |
| PMCID: | PMC2827875 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 30 November 2010" - "CODEN: NMBIE" - "Source: Scopus" |
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