Ac-EAZY! Towards GMP-Compliant Module Syntheses of (225)Ac-Labeled Peptides for Clinical Application

The application of (225)Ac (half-life T(1/2) = 9.92 d) dramatically reduces the activity used for peptide receptor radionuclide therapy by a factor of 1000 in comparison to (90)Y, (177)Lu or (188)Re while maintaining the therapeutic outcome. Additionally, the range of alpha particles of (225)Ac and its daughter nuclides in tissue is much lower (47–85 μm for alpha energies E(α) = 5.8–8.4 MeV), which results in a very precise dose deposition within the tumor. DOTA-conjugated commercially available peptides used for endoradiotherapy, which can readily be labeled with (177)Lu or (90)Y, can also accommodate (225)Ac. The benefits are lower doses in normal tissue for the patient, dose reduction of the employees and environment and less shielding material. The low availability of (225)Ac activity is preventing its application in clinical practice. Overcoming this barrier would open a broad field of (225)Ac therapy. Independent which production pathway of (225)Ac proves the most feasible, the use of automated synthesis and feasible and reproducible patient doses are needed. The Modular-Lab EAZY is one example of a GMP-compliant system, and the cassettes used for synthesis are small. Therefore, also the waste after the synthesis can be minimized. In this work, two different automated setups with different purification systems are presented. In its final configuration, three masterbatches were performed on the ML EAZY for DOTA-TATE and PSMA-I&T, respectively, fulfilling all quality criteria with final radiochemical yields of 80–90% for the (225)Ac-labeled peptides.