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

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 activities (ESA) and bindable metals concentrations ([M_B]) that exceed those reported by the traditional single hydroxamate column method.