Graduate Project

Purification of cyclotron-produced 89Zr for its use in diagnostic radiopharmaceutical labeling

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  • Production of 89Zr serves as a crucial preliminary step for exploring Zr-chelates, determining their stability constants, and advancing radiolabeling methodologies for monoclonal antibody based theranostics. 89Zr is typically produced by the irradiation of natural yttrium targets, a process extensively documented in scientific literature. Two primary methods are employed: the 89Y(p,n)89Zr and 89Y(d,2n)89Zr reactions, both offering favorable cross-section values achievable within the energy range of small medical cyclotrons. Given the prevalent use of the (p,n) reaction in prior studies, we developed a 89Zr production and purification protocol for a medical isotope research facility involving approximately 14.5 MeV proton bombardment of natural yttrium foils from a GE PETrace 800 using a modified Comecer Solid Target Transfer system. After bombardment of natural yttrium foils, purification of 89Zr from its parent 89Y, as well as byproducts of the nuclear reaction such as 88Y and 88Zr, alongside contaminants originating from the dissolved target holder (e.g., Fe, Cu, Zn, Al), was accomplished through a sequential anion-exchange and chelating resin process. Initially, the irradiated yttrium target underwent dissolution in hydrochloric acid. The resulting solution was then loaded onto a strong anion exchange resin, AG-MP 1M resin, followed by subsequent purification steps involving a hydroxamate-functionalized resin derived from a weak cation-exchange resin, Accell Plus CM. After loading and rinsing, elution of the target material was accomplished using oxalic acid. The eluted Zr-oxalate was subsequently transchelated to form the Zr-DFO complex, a pivotal step preparing the radionuclide for binding with antibodies. This meticulously executed procedure ensures the acquisition of highly purified 89Zr, devoid of contaminants, suitable for subsequent applications in radiopharmaceutical research and development.
  • KEYWORDS: isotope production for antibody radiolabeling, zirconium-89 cyclotron production, zirconium-89 purification, zirconium-89, hydroxamate resin synthesis
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