Separation of (44)Sc from (44)Ti in the Context of A Generator System for Radiopharmaceutical Purposes with the Example of [(44)Sc]Sc-PSMA-617 and [(44)Sc]Sc-PSMA-I&T Synthesis

Today, (44)Sc is an attractive radionuclide for molecular imaging with PET. In this work, we evaluated a (44)Ti/(44)Sc radionuclide generator based on TEVA resin as a source of (44)Sc. The generator prototype (5 MBq) exhibits high (44)Ti retention and stable yield of (44)Sc (91 ± 6 %) in 1 mL of eluate (20 bed volumes, eluent—0.1 M oxalic acid/0.2 M HCl) during one year of monitoring (more than 120 elutions). The breakthrough of (44)Ti did not exceed 1.5 × 10(−5)% (average value was 6.5 × 10(−6)%). Post-processing of the eluate for further use in radiopharmaceutical synthesis was proposed. The post-processing procedure using a combination of Presep(®) PolyChelate and TK221 resins made it possible to obtain (44)Sc-radioconjugates with high labeling yield (≥95%) while using small precursor amounts (5 nmol). The proposed method takes no more than 15 min and provides ≥90% yield relative to the (44)Sc activity eluted from the generator. The labeling efficiency was demonstrated on the example of [(44)Sc]Sc-PSMA-617 and [(44)Sc]Sc-PSMA-I&T synthesis. Some superiority of PSMA-I&T over PSMA-617 in terms of (44)Sc labeling efficiency was demonstrated (likely due to presence of DOTAGA chelator in the precursor structure). It was also shown that microwave heating of the reaction mixture considerably shortened the reaction time and improved radiolabeling yield and reproducibility of [(44)Sc]Sc-PSMA-617 and [(44)Sc]Sc-PSMA-I&T synthesis.