Automated synthesis of [ 89 Zr]ZrCl 4 , [ 89 Zr]ZrDFOSquaramide-bisPh(PSMA) and [ 89 Zr]ZrDFOSquaramide-TATE.

Background: Automated [ ⁸⁹ Zr]Zr-radiolabeling processes have the potential to streamline the production of [ ⁸⁹ Zr]Zr-labelled PET imaging agents. Most radiolabeling protocols use [ ⁸⁹ Zr][Zr(ox) ₄ ] ^4- as the starting material and oxalate is removed after radiolabeling. In some instances, radiolabeling with [ ⁸⁹ Zr]ZrCl ₄ as starting material gives better radiochemical yields at lower reaction temperatures. In this work, a fully-automated process for production of [ ⁸⁹ Zr]ZrCl ₄ is reported and its use for the synthesis of [ ⁸⁹ Zr]ZrDFOSq-bisPhPSMA and [ ⁸⁹ Zr]ZrDFOSq-TATE.
Results: A simple automated process for the isolation of [ ⁸⁹ Zr]ZrCl ₄ by trapping [ ⁸⁹ Zr][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. [ ⁸⁹ Zr]ZrCl ₄ was routinely recovered from [ ⁸⁹ Zr][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 [ ⁸⁹ Zr]ZrCl ₄ was neutralized with sodium acetate buffer (0.25 M) removing the requirement for cumbersome manual neutralization with strong base. The mixture of [ ⁸⁹ Zr]ZrCl ₄ was used for direct automated radiolabeling reactions to produce [ ⁸⁹ Zr]Zr-DFOSquaramide-bisPhPSMA and [ ⁸⁹ Zr]ZrDFOSquaramide-TATE in 80-90% over all RCY in > 95% RCP.
Conclusions: This method for the production of [ ⁸⁹ Zr]ZrCl ₄ does not require removal of HCl by evaporation making this process relatively fast and efficient. The fully automated procedures for the production of [ ⁸⁹ Zr]ZrCl ₄ and its use in radiolabeling are well suited to support the centralized and standardized manufacture of multiple dose preparations of zirconium-89 based radiopharmaceuticals.
(© 2024. The Author(s).)