Compact accelerator-based production of carrier-free ¹⁷⁷Lu from 18 MeV D + on [¹⁷⁶Yb] Yb 2 O 3

Recent EMA and FDA approvals of Lu-DOTATATE and Lu-PSMA-617 have led to increased demand for radiotherapeutic $_{}^{177}$ 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 $_{}^{177}$ Lu using a 10 mA, 18 MeV $D^{+}$ 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 $12\text{m}$ . Deuteron activations on a 99% enriched [ $_{}^{176}$ Yb] ${\text{Yb}}_2{\text{O}}_3$ target are estimated using experimental and simulated excitation functions.

A circular target with a radius of 1 cm and 0.36 mm thickness is selected to optimize the yield of $_{}^{177}$ Lu while minimizing the production of undesirable radioisotopes, including $_{}^{174g+m}$ Lu and $_{}^{177m}$ Lu. Model calculations indicate that the accelerator design can produce 11.3 μg of $_{}^{177}$ Lu per hour. A 5-day irradiation is expected to yield approximately 1.07 mg of $_{}^{177}$ 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 ${\text{Yb}}_2{\text{O}}_3$ target suggests it may be recycled and reused over multiple irradiations.

The study confirms the feasibility of accelerator-based $_{}^{177}$ Lu production as an alternative to existing reactor-based methods. The 10 mA, 18 MeV $D^{+}$ RFQ-DTL design achieves an exceptionally high $_{}^{177}$ Lu radiopurity and a competitive overall yield, which can meet the dose requirements of thousands of patients.