Anion exchange and extraction chromatography tandem column isolation of zirconium-89 (89Zr) from cyclotron bombarded targets using an automated fluidic platform

• Published in: Journal of Chromatography 2022-08, Vol.1678 (C), p.463347, Article 463347
• Main Authors: O'Hara, Matthew J., Carter, Jennifer C., Kellogg, Cynthia M., Link, Jeanne M.
• Format: Article
• Language: English
• Subjects: Di-(2-ethylhexyl)phosphoric acid; HDEHP; immunoPET; Laboratory automation; LN Resin
• ISSN: 0021-9673
• DOI: 10.1016/j.chroma.2022.463347

•Zr(IV), Y(III), and Fe(III) Kd on LN resin across a range of HCl is reported.•Zr(IV) Kd on LN resin in acidic chloride and fluoride solutions are reported.•Zr(IV) Kd on LN resin across a range of oxalic acid is reported.•A tandem column 89Zr purification process is demonstrated using a fluidic system.•End-to-end 89Zr purification is demonstrated using seven cyclotron bombarded Y metal targets.•89Zr product quality determined by transchelation titrations with deferoxamine mesylate salt; results compared to literature values. The long-lived positron emitter 89Zr is a highly promising nuclide employed in diagnostic Positron Emission Tomography (PET) imaging. Methods of radiochemical processing to obtain 89Zr for clinical use are traditionally performed with a single hydroxamate resin column. Herein, we present a tandem column purification method for the preparation of high-purity 89Zr from cyclotron bombarded natural Y metal foils. The primary column is a macroporous, strongly basic anion exchange resin on styrene divinylbenzene co-polymer. The secondary microcolumn, with an internal volume of 33 μL, is packed with an extraction chromatography resin (ExCR) loaded with di-(2-ethylhexyl)phosphoric acid (HDEHP). A condition of “inverted selectivity” is presented, wherein the 89Zr elution from the primary column is synonymous with the load condition on the secondary column. The ability to transfer 89Zr from one column to the next allows two sequential purification steps to be performed prior to the final elution of the 89Zr product. This approach assures delivery of high purity 89Zr. The tandem column purification process has been implemented into a prototype automated fluidic system. Optimization of the method is presented, followed by evaluation of the process using seven cyclotron bombarded Y metal foil targets. Once optimized, we found that 93.7 ± 2.3% of the 89Zr present in the foils was recovered in the secondary column elution fraction (0.8 M oxalic acid). Radiochromatograms of the product elution peaks enabled determination of full width at half-maximum (FWHM) and 89Zr collection yields as a function of volume. Because of the small size of the secondary microcolumn, a 89Zr product volume of ∼0.28 mL is reported, which provides a substantially increased nuclide concentration over traditional methods. Finally, we evaluated the transchelation of the resulting 89Zr oxalate product to deferoxamine mesylate (DFOM) salt. We observed effective specific activitie