Evaluation of a chloride-based 89Zr isolation strategy using a tributyl phosphate (TBP)-functionalized extraction resin

Nucl Med Biol. 2018 Sep-Oct:64-65:1-7. doi: 10.1016/j.nucmedbio.2018.06.003. Epub 2018 Jun 18.

Abstract

Introduction: The remarkable stability of the 89Zr-DOTA complex has been shown in recent literature. The formation of this complex appears to require 89Zr-chloride as the complexation precursor rather than the more conventional 89Zr-oxalate. In this work we present a method for the direct isolation of 89Zr-chloride from irradiated natY foils.

Methods: 89Zr, 88Zr, and 88Y were prepared by 16 MeV proton irradiation of natY foils and used for batch-extraction based equilibrium coefficient measurements for TBP and UTEVA resin. Radionuclidically pure 89Zr was prepared by 14 MeV proton-irradiation of natY foils. These foils were dissolved in concentrated HCl, trapped on columns of TBP or UTEVA resin, and 89Zr-chloride was eluted in <1 mL of 0.1 M HCl. For purposes of comparison, conventionally-isolated 89Zr-oxalate was converted to 89Zr-chloride by trapping, rinsing, and elution from a QMA cartridge into 1 M HCl. Trace metal analysis was performed on the resulting 89Zr products.

Results: Equilibrium coefficients for Y and Zr were similar between UTEVA and TBP resins across all HCl concentrations. Kd values of <10-1 mL/g were observed for Y across all HCl concentrations. Kd values of >103 mL/g were observed at HCl concentrations >9 M for Zr, falling to Kd values of <100 mL/g at low HCl concentrations. 89Zr-chloride was recovered from small columns of TBP in <1 mL of 0.1 M HCl with an overall recovery efficiency of 89 ± 3% (n = 3). An average Y/Zr separation factor of 1.5 × 105 (n = 3) was obtained. Trace metal impurities, notably Fe, were higher in TBP-isolated 89Zr-chloride compared with 89Zr-chloride prepared using the conventional two-step procedure.

Conclusion: TBP-functionalized resin appears promising for the direct isolation of 89Zr-chloride from irradiated natY targets. Excellent 89Zr recovery efficiencies were obtained, and chemical purity was sufficient for proof-of-concept chelation studies.

Keywords: Positron emission tomography; Zirconium-89; immunoPET; zr89.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chlorides / chemistry*
  • Cyclotrons
  • Deferoxamine / chemistry
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Organophosphates / chemistry*
  • Radiochemistry / instrumentation
  • Radiochemistry / methods*
  • Radioisotopes / chemistry*
  • Radioisotopes / isolation & purification*
  • Resins, Synthetic / chemistry*
  • Zirconium / chemistry*
  • Zirconium / isolation & purification*

Substances

  • Chlorides
  • Heterocyclic Compounds, 1-Ring
  • Organophosphates
  • Radioisotopes
  • Resins, Synthetic
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • tributyl phosphate
  • Zirconium
  • Deferoxamine
  • Zirconium-89