Automated synthesis of [89Zr]ZrCl4, [89Zr]ZrDFOSquaramide-bisPh(PSMA) and [89Zr]ZrDFOSquaramide-TATE

Abstract

Abstract Background Automated [89Zr]Zr-radiolabeling processes have the potential to streamline the production of [89Zr]Zr-labelled PET imaging agents. Most radiolabeling protocols use [89Zr][Zr(ox)4]4− as the starting material and oxalate is removed after radiolabeling. In some instances, radiolabeling with [89Zr]ZrCl4 as starting material gives better radiochemical yields at lower reaction temperatures. In this work, a fully-automated process for production of [89Zr]ZrCl4 is reported and its use for the synthesis of [89Zr]ZrDFOSq-bisPhPSMA and [89Zr]ZrDFOSq-TATE. Results A simple automated process for the isolation of [89Zr]ZrCl4 by trapping [89Zr][Zr(ox)4]4− on a bicarbonate-activated strong anion exchange cartridge followed by elution with 0.1 M HCl in 1 M NaCl was developed. [89Zr]ZrCl4 was routinely recovered from [89Zr][Zr(ox)4]4− in > 95% yield in mildly acidic solution of 0.1 M HCl in 1 M NaCl using a fully-automated process. The [89Zr]ZrCl4 was neutralized with sodium acetate buffer (0.25 M) removing the requirement for cumbersome manual neutralization with strong base. The mixture of [89Zr]ZrCl4 was used for direct automated radiolabeling reactions to produce [89Zr]Zr-DFOSquaramide-bisPhPSMA and [89Zr]ZrDFOSquaramide-TATE in 80–90% over all RCY in > 95% RCP. Conclusions This method for the production of [89Zr]ZrCl4 does not require removal of HCl by evaporation making this process relatively fast and efficient. The fully automated procedures for the production of [89Zr]ZrCl4 and its use in radiolabeling are well suited to support the centralized and standardized manufacture of multiple dose preparations of zirconium-89 based radiopharmaceuticals.

Keywords

• Zirconium-89
• Radiopharmaceuticals
• Automated synthesis
• [89Zr]ZrCl4