Theoretical investigation of alternative 177Lu production methods using proton accelerator: A Monte Carlo study

This study presents a theoretical assessment of ¹⁷⁷Lu production using proton accelerator-driven neutron generators with light- and medium-mass target materials. Both the direct route, via neutron activation of ¹⁷⁶Lu, and the indirect route, via activation of ¹⁷⁶Yb, were evaluated for proton energies up to 18 MeV. Monte Carlo simulations with PHITS coupled to DCHAIN were used to model neutron yields, energy spectra, and activation efficiencies for neutron generators composed of H₂¹⁸O, ^natBe, ^natLi, ^natCr, and ^natTi. Results identify ^natBe as the most efficient neutron generator, delivering the highest ¹⁷⁷Lu activities in both production routes. H₂¹⁸O provides superior radionuclidic purity in the direct route due to its moderated neutron spectrum, while ^natTi achieves the highest n.c.a. ¹⁷⁷Lu activity in the indirect route. ^natTi and ^natCr offer intermediate yields with fewer handling hazards. Clinical implementation scenarios indicate that ¹⁷⁷Lu production via the direct route is feasible using ^natBe at 18 MeV for maximum yield (≥500 μA, ≤7 days per patient dose) or H₂¹⁸O at 15 MeV for optimized purity (≥1 mA, ≤10 days per patient dose). While these findings demonstrate the potential of compact, accelerator-driven neutron generator systems as scalable and decentralized alternatives to reactor-based ¹⁷⁷Lu production, further research is required to validate scalability, target thermal management, and economic viability for high-volume clinical deployment.