Compact accelerator-based production of carrier-free 177Lu from 18 MeV D⁺ on [176Yb]Yb₂O₃

Background Recent EMA and FDA approvals of Lu-DOTATATE and Lu-PSMA-617 have led to increased demand for radiotherapeutic ¹⁷⁷ 177 Lu, due to its promising potential to treat castration-resistant neuroendocrine cancers. Conventional reactor production methods pose challenges related to cost, waste management, and local availability. In comparison, accelerators produce less waste, have lower maintenance costs, and can be directly integrated into hospital settings. In this study, we evaluate the production of radiotherapeutic ¹⁷⁷ 177 Lu using a 10 mA, 18 MeV D⁺ D + compact linear accelerator design. The design consists of a single radio-frequency quadrupole (RFQ) and seven drift tube linacs (DTLs) that achieve a beam efficiency of 98.5% over a total length of 12\,m 12 m . Deuteron activations on a 99% enriched [ ¹⁷⁶ 176 Yb] Yb₂O₃ Yb 2 O 3 target are estimated using experimental and simulated excitation functions. Results A circular target with a radius of 1 cm and 0.36 mm thickness is selected to optimize the yield of ¹⁷⁷ 177 Lu while minimizing the production of undesirable radioisotopes, including ¹⁷⁴ᵍ⁺ᵐ 174 g + m Lu and ¹⁷⁷ᵐ 177 m Lu. Model calculations indicate that the accelerator design can produce 11.3 μg of ¹⁷⁷ 177 Lu per hour. A 5-day irradiation is expected to yield approximately 1.07 mg of ¹⁷⁷ 177 Lu (4.4 TBq), while a 12-day irradiation can produce up to 1.9 mg (7.8 TBq). Following a 2-day processing period, the specific activity of the 5-day irradiated sample is projected to approach 0.6 TBq/mg, with a radiopurity of approximately 99.8%. The minimal burn-up of the Yb₂O₃ Yb 2 O 3 target suggests it may be recycled and reused over multiple irradiations. Conclusions The study confirms the feasibility of accelerator-based ¹⁷⁷ 177 Lu production as an alternative to existing reactor-based methods. The 10 mA, 18 MeV D⁺ D + RFQ-DTL design achieves an exceptionally high ¹⁷⁷ 177 Lu radiopurity and a competitive overall yield, which can meet the dose requirements of thousands of patients.