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