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

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.