Hydroxamate column-based purification of zirconium-89 (⁸⁹Zr) using an automated fluidic platform

Zirconium-89 (⁸⁹Zr) is a long-lived (t_1/2 = 78.4h) positron-emitting isotope that is useful for positron emission tomography (PET) based diagnostic imaging using radiolabeled antibodies. Hydroxamate resin columns are predominantly used for the purification of ⁸⁹Zr from cyclotron bombarded ^natY targets dissolved in strong HCl. ⁸⁹Zr is conventionally eluted from the resin in 1M oxalic acid (H₂C₂O₄), a complexant that is conducive to follow-on binding of ⁸⁹Zr through a transchelation process to the deferoxamine siderophore. In the present study, we determined that a lower concentration of H₂C₂O₄ eluent (0.8M) is adequate to efficiently remove ⁸⁹Zr from a column containing 100mg hydroxamate resin. As a result, less buffering agents are needed to be added to the ⁸⁹Zr product fraction prior to labeling. A simple automated fluidic system prototype has been developed to perform the steps required for ⁸⁹Zr purification using a hydroxamate resin column (column conditioning in HCl, Y target dissolution, dissolved target solution load onto column, column washes using HCl and water, and ⁸⁹Zr elution). The system performance was evaluated using several cyclotron bombarded Y targets; ⁸⁹Zr product fractions demonstrated excellent chemical recoveries from these targets, with 1.0mL product volumes yielding 89±2% of the column elution peak activity and 84±2% of ⁸⁹Zr recovered from the target (at EOB). These results compare favorably with previously published ⁸⁹Zr product volumes and yields, despite the lower concentration of H₂C₂O₄ eluent employed. Transchelation of resulting ⁸⁹Zr product fractions was performed to assess product quality. The effective specific activity (ESA) ranged between 44(7) and 109(22) TBq·mmole^-1, while the bindable metals concentration, a metric introduced for assessing and comparing product purity, ranged between 43(7) and 115(27) nmole·g^-1.