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

The long-lived positron emitter Zr is a highly promising nuclide employed in diagnostic Positron Emission Tomography (PET) imaging. Methods of radiochemical processing to obtain Zr 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 Zr 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 Zr elution from the primary column is synonymous with the load condition on the secondary column. The ability to transfer Zr from one column to the next allows two sequential purification steps to be performed prior to the final elution of the Zr product. This approach assures delivery of high purity Zr. 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 Zr 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 Zr collection yields as a function of volume. Because of the small size of the secondary microcolumn, a Zr 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 Zr oxalate product to deferoxamine mesylate (DFOM) salt. We observed effective specific activities (ESA) and bindable metals concentrations ([M]) that exceed those reported by the traditional single hydroxamate column method.