Morris Austin A, Wei Tianhao, Wang Zhi, Xia Ying, Han Meiyun, Lu Yuanrong
State Key Laboratory of Nuclear Physics and Technology, Peking University, 5 Yiheyuan Rd., Beijing, 100871, China.
EJNMMI Radiopharm Chem. 2025 Aug 25;10(1):56. doi: 10.1186/s41181-025-00358-3.
Recent EMA and FDA approvals of Lu-DOTATATE and Lu-PSMA-617 have led to increased demand for radiotherapeutic 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 Lu using a 10 mA, 18 MeV 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 . Deuteron activations on a 99% enriched [ Yb] 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 Lu while minimizing the production of undesirable radioisotopes, including Lu and Lu. Model calculations indicate that the accelerator design can produce 11.3 μg of Lu per hour. A 5-day irradiation is expected to yield approximately 1.07 mg of 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 target suggests it may be recycled and reused over multiple irradiations.
The study confirms the feasibility of accelerator-based Lu production as an alternative to existing reactor-based methods. The 10 mA, 18 MeV RFQ-DTL design achieves an exceptionally high Lu radiopurity and a competitive overall yield, which can meet the dose requirements of thousands of patients.
欧洲药品管理局（EMA）和美国食品药品监督管理局（FDA）最近批准了镥[¹⁷⁷Lu]DOTATATE和镥[¹⁷⁷Lu]PSMA - 617，由于其在治疗去势抵抗性神经内分泌癌方面具有广阔前景，对放射性治疗用镥的需求不断增加。传统反应堆生产方法在成本、废物管理和本地可获得性方面存在挑战。相比之下，加速器产生的废物更少，维护成本更低，并且可以直接集成到医院环境中。在本研究中，我们评估了使用一台10 mA、18 MeV紧凑型直线加速器设计生产放射性治疗用镥的情况。该设计由一个单射频四极杆（RFQ）和七个漂移管直线加速器（DTL）组成，在总长度为[具体长度未给出]的情况下实现了98.5%的束流效率。使用实验和模拟激发函数估算了在99%富集的[¹⁷⁶Yb]靶上的氘核活化情况。
选择半径为1 cm、厚度为0.36 mm的圆形靶来优化镥的产量，同时尽量减少不期望的放射性同位素（包括¹⁷⁶Lu和¹⁷⁸Lu）的产生。模型计算表明，该加速器设计每小时可生产11.3 μg的镥。预计5天的辐照可产生约1.07 mg的镥（4.4 TBq），而12天的辐照可产生高达1.9 mg（7.8 TBq）。经过2天的处理期，5天辐照样品的比活度预计接近0.6 TBq/mg，放射性纯度约为99.8%。靶的最小燃耗表明它可能在多次辐照中回收再利用。
该研究证实了基于加速器生产镥作为现有基于反应堆方法的替代方案的可行性。10 mA、18 MeV的RFQ - DTL设计实现了极高的镥放射性纯度和具有竞争力的总体产量，能够满足数千名患者的剂量需求。
