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

Background: Automated [Zr]Zr-radiolabeling processes have the potential to streamline the production of [Zr]Zr-labelled PET imaging agents. Most radiolabeling protocols use [Zr][Zr(ox)] as the starting material and oxalate is removed after radiolabeling. In some instances, radiolabeling with [Zr]ZrCl as starting material gives better radiochemical yields at lower reaction temperatures. In this work, a fully-automated process for production of [Zr]ZrCl is reported and its use for the synthesis of [Zr]ZrDFOSq-bisPhPSMA and [Zr]ZrDFOSq-TATE.

Results: A simple automated process for the isolation of [Zr]ZrCl by trapping [Zr][Zr(ox)] on a bicarbonate-activated strong anion exchange cartridge followed by elution with 0.1 M HCl in 1 M NaCl was developed. [Zr]ZrCl was routinely recovered from [Zr][Zr(ox)] in > 95% yield in mildly acidic solution of 0.1 M HCl in 1 M NaCl using a fully-automated process. The [Zr]ZrCl was neutralized with sodium acetate buffer (0.25 M) removing the requirement for cumbersome manual neutralization with strong base. The mixture of [Zr]ZrCl was used for direct automated radiolabeling reactions to produce [Zr]Zr-DFOSquaramide-bisPhPSMA and [Zr]ZrDFOSquaramide-TATE in 80-90% over all RCY in > 95% RCP.

Conclusions: This method for the production of [Zr]ZrCl does not require removal of HCl by evaporation making this process relatively fast and efficient. The fully automated procedures for the production of [Zr]ZrCl and its use in radiolabeling are well suited to support the centralized and standardized manufacture of multiple dose preparations of zirconium-89 based radiopharmaceuticals.