Radiopharmaceutical Quality Control Considerations for Accelerator-Produced Actinium Therapies.

Abstract

Background: Alpha-particle-emitting radiotherapies are of great interest for the treatment of disseminated cancer. Actinium-225 (225Ac) produces four α-particles through its decay and is among the most attractive radionuclides for use in targeted radiotherapy applications. However, supply issues for this isotope have limited availability and increased cost for research and translation. Efforts have focused on accelerator-based methods that produce 225Ac in addition to long-lived 227Ac. Objective: The authors investigated the impact of 225Ac/227Ac material in the radiolabeling and radiopharmaceutical quality control evaluation of a DOTA chelate-conjugated peptide under good manufacturing practices. The authors use an automated module under identical conditions with either generator or accelerator-produced actinium radiolabeling. Methods: The authors have performed characterization of the radiolabeled products, including thin-layer chromatography, high-pressure liquid chromatography, gamma counting, and high-energy resolution gamma spectroscopy. Results: Peptide was radiolabeled and assessed at >95% radiochemical purity with high yields for generator produced 225Ac. The radiolabeling results produced material with subtle but detectable differences when using 225Ac/227Ac. Gamma spectroscopy was able to identify peptide initially labeled with 227Th, and at 100 d for quantification of 225Ac-bearing peptide. Conclusion: Peptides produced using 225Ac/227Ac material may be suitable for translation, but raise new issues that include processing times, logistics, and contaminant detection.