对于不对[177Lu]Lu-PSMA疗法有反应的晚期转移性去势抵抗性前列腺癌（mCRPC）患者，有效的治疗选择有限。通过[225Ac]Ac-PSMA获得的临床结果是很有前景的。我们回顾性分析了2018年12月至2022年10月接受[225Ac]Ac-PSMA治疗的患者的疗效。方法：我们评估了23例mCRPC患者（平均年龄70.3±8.8岁）在[177Lu]Lu-PSMA治疗（2-9个疗程）失败后的治疗结果。根据CTCAE 5.0标准评估其安全性。根据前列腺特异性膜抗原PET进展标准和前列腺特异性抗原（PSA）响应（根据前列腺癌工作组2标准）评估第一个[225Ac]Ac-PSMA疗程后的治疗疗效。结果：所有患者均接受了去势治疗，其中22例（96%）和19例（83%）患者分别接受了化疗和二代抗雄激素治疗。其中1例患者接受了4个疗程，2例接受了3个疗程，8例接受了2个疗程，12例接受了1个疗程的[225Ac]Ac-PSMA治疗。疗程间隔的中位数为13周（范围为8-28周）。每个疗程中[225Ac]Ac-PSMA的平均活度为7.6 MBq（范围为6.2-10.0 MBq）。患者处于晚期疾病阶段，肿瘤负担非常高。尽管在[225Ac]Ac-PSMA治疗后，5例患者（26%）表现出最佳的PSA响应，但在11例患者（58%; n = 19）中观察到了至少某种程度的PSA下降。治疗反应经过[68Ga]Ga-PSMA PET/CT成像的患者进行了评估。在第一个疗程后（n = 18），根据前列腺特异性膜抗原PET进展标准，有50%的患者（n = 9）显示疾病进展，疾病控制率计算结果为50%。无进展生存中位数为3.1个月，总生存中位数为7.7个月。有1例患者出现3级血液系统毒性反应，另1例患者出现3级肾毒性。虽然所有患者在治疗前都有口干症状，但腮腺SUVmax减少了33%。结论：我们观察到，即使在完成了其他所有治疗选择的晚期转移性去势抵抗性前列腺癌（mCRPC）患者中，[225Ac]Ac-PSMA疗法仍安全有效，显示出潜力。© 2023年由核医学与分子影像学学会发表。

For patients with advanced-stage metastatic castration-resistant prostate cancer (mCRPC) who do not respond to [177Lu]Lu-PSMA therapy, there are limited treatment options. Clinical results obtained with [225Ac]Ac-PSMA are promising. We retrospectively analyzed the outcomes of patients treated with [225Ac]Ac-PSMA between December 2018 and October 2022. Methods: We evaluated the treatment results of 23 patients (mean age, 70.3 ± 8.8 y) with mCRPC who were refractory to treatment with [177Lu]Lu-PSMA (2-9 cycles). The safety profile was assessed according to Common Technology Criteria for Adverse Events version 5.0. Treatment efficacy was assessed using prostate-specific membrane antigen PET progression criteria and prostate-specific antigen (PSA) response according to Prostate Cancer Working Group 2 criteria after the first cycle of [225Ac]Ac-PSMA treatment. Results: All patients received androgen-deprivation therapy, whereas 22 (96%) and 19 (83%) patients received chemotherapy and second-generation antiandrogen therapy, respectively. One patient received 4 cycles, 2 received 3 cycles, 8 received 2 cycles, and 12 received 1 cycle of [225Ac]Ac-PSMA. The median interval between cycles was 13 wk (range, 8-28 wk). [225Ac]Ac-PSMA was administered with a mean activity of 7.6 MBq (range, 6.2-10.0 MBq) in each cycle. Patients were at an advanced stage of disease, and tumor burden was very high. Although the best PSA response was observed in 5 patients (26%) after [225Ac]Ac-PSMA treatment, there was at least some level of decline in PSA observed in 11 patients (58%; n = 19). Treatment response was assessed in patients who underwent [68Ga]Ga-PSMA PET/CT imaging. After the first cycle of treatment (n = 18), 50% of patients (n = 9) showed disease progression according to prostate-specific membrane antigen PET progression criteria, and the disease control rate was calculated to be 50%. Median progression-free survival was 3.1 mo, and median overall survival was 7.7 mo. Grade 3 hematologic toxicity occurred in 1 patient, and grade 3 nephrotoxicity was observed in another patient. Parotid SUVmax decreased by 33%, although all patients complained of dry mouth before treatment. Conclusion: We observed that [225Ac]Ac-PSMA therapy was safe and showed potential even in cases with advanced-stage mCRPC in which all other treatment options were completed.© 2023 by the Society of Nuclear Medicine and Molecular Imaging.