Radiopharmaceutical Quality Control Considerations for Accelerator-Produced Actinium Therapies

Background: Alpha-particle-emitting radiotherapies are of great interest for the treatment of disseminated cancer. Actinium-225 (Ac-225) produces four alpha-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 Ac-225 in addition to long-lived Ac-227.Objective: The authors investigated the impact of Ac-225/Ac-227 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 Ac-225. The radiolabeling results produced material with subtle but detectable differences when using Ac-225/Ac-227. Gamma spectroscopy was able to identify peptide initially labeled with Th-227, and at 100 d for quantification of Ac-225-bearing peptide.Conclusion: Peptides produced using Ac-225/Ac-227 material may be suitable for translation, but raise new issues that include processing times, logistics, and contaminant detection.

Automated summary

The study investigated the impact of Ac-225/Ac-227 material in radiolabeling and quality control evaluation, showing that peptides produced using generator produced Ac-225 can be radiolabeled efficiently. There were subtle but detectable differences in material produced using Ac-225/Ac-227.