Optimization of Ra-225/Ac-225 Production via Proton Spallation on Thorium: Physical Evaluation of Beam Energy and Target Thickness

摘要: Actinium-225 (Ac-225) is a promising radionuclide for targeted alpha therapy, but its global supply remains critically constrained. Since proton spallation on thorium targets serves as a vital complementary production pathway, the reliability of cross-section data and the associated optimization methodology are essential for developing an irradiation scheme. We employed simulations validated against experimental data to obtain reliable cross-sections for Ac-225 and its precursors. A multi-objective optimization methodology was developed for cost-effective Ac-225 and its precursor Radium-225 (Ra-225) production. Yield per Unit Target Mass (YUTM) and Yield per Unit Beam Power (YUBP) are newly introduced to enable simultaneous optimization of thick target yield (TTY), target mass usage, and beam power utilization. The irradiation parameters were optimized over a proton energy range of 5–1000 MeV and target thicknesses up to 500 mm. For Ac-225, jointly optimizing TTY and target mass usage yields 250 MeV with a 60-mm target thickness, while optimizing TTY and beam power utilization yields 340 MeV with 97.5 mm. For Ra-225, the optimal energies shift higher, with beam power utilization optimized at 400 MeV and target mass usage optimized at 530 MeV. Generator elution analysis was carried out to characterize the evolution of Ac-225. Thermal management analysis indicates that incident energies exceeding 300 MeV position the Bragg peak beyond the optimized target thickness. The optimization methodology and associated cross-section information provide a reference for isotope-production physics and practical guidance for designing new production projects.