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

Matthew J. O'Hara, Nathaniel J. Murray, Jennifer C. Carter, Cynthia M. Kellogg, Jeanne M. Link

Research output: Contribution to journalArticle

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Abstract

Zirconium-89 (89Zr) is a long-lived (t1/2 = 78.4 h) 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 1 M 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 (0.8 M) is adequate to efficiently remove 89Zr from a column containing 100 mg 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 1.0 mL 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.

LanguageEnglish (US)
Pages85-94
Number of pages10
JournalApplied Radiation and Isotopes
Volume132
DOIs
StatePublished - Feb 1 2018

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fluidics
purification
platforms
resins
products
elution
cyclotrons
low concentrations
positrons
oxalic acid
conditioning
antibodies
marking
dissolving
purity
isotopes
tomography
recovery
prototypes
metals

Keywords

  • Zr
  • Deferoxamine
  • Hydroxamate
  • ImmunoPET
  • Laboratory automation
  • Medical isotope
  • Zirconium-89

ASJC Scopus subject areas

  • Radiation

Cite this

Hydroxamate column-based purification of zirconium-89 (89Zr) using an automated fluidic platform. / O'Hara, Matthew J.; Murray, Nathaniel J.; Carter, Jennifer C.; Kellogg, Cynthia M.; Link, Jeanne M.

In: Applied Radiation and Isotopes, Vol. 132, 01.02.2018, p. 85-94.

Research output: Contribution to journalArticle

O'Hara, Matthew J. ; Murray, Nathaniel J. ; Carter, Jennifer C. ; Kellogg, Cynthia M. ; Link, Jeanne M./ Hydroxamate column-based purification of zirconium-89 (89Zr) using an automated fluidic platform. In: Applied Radiation and Isotopes. 2018 ; Vol. 132. pp. 85-94
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AB - Zirconium-89 (89Zr) is a long-lived (t1/2 = 78.4 h) 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 1 M 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 (0.8 M) is adequate to efficiently remove 89Zr from a column containing 100 mg 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 1.0 mL 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.

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