Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany
Directorate for Nuclear Safety and Security, European Commission, Joint Research Centre, Karlsruhe, Germany.
J Nucl Med. 2017 Oct;58(10):1624-1631. doi: 10.2967/jnumed.117.191395. Epub 2017 Apr 13.
The aim of this study was to develop a treatment protocol for Ac-PSMA-617 α-radiation therapy in advanced-stage, metastatic castration-resistant prostate cancer patients with prostate-specific membrane antigen (PSMA)-positive tumor phenotype. A dosimetry estimate was calculated on the basis of time-activity curves derived from serially obtained Lu-PSMA-617 scans extrapolated to the physical half-life of Ac, assuming instant decay of unstable daughter nuclides. Salvage therapies empirically conducted with 50 ( = 4), 100 ( = 4), 150 ( = 2), and 200 kBq/kg ( = 4) of Ac-PSMA-617 were evaluated retrospectively regarding toxicity and treatment response. Eight of 14 patients received further cycles in either 2- or 4-mo intervals with identical or deescalated activities. Dosimetry estimates for 1 MBq of Ac-PSMA-617 assuming a relative biologic effectiveness of 5 revealed mean doses of 2.3 Sv for salivary glands, 0.7 Sv for kidneys, and 0.05 Sv for red marrow that are composed of 99.4% α, 0.5% β, and 0.1% photon radiation, respectively. In clinical application, severe xerostomia became the dose-limiting toxicity if treatment activity exceeded 100 kBq/kg per cycle. At 100 kBq/kg, the duration of prostate-specific antigen decline was less than 4 mo, but if therapy was repeated every 2 mo patients experienced additive antitumor effects. Treatment activities of 50 kBq/kg were without toxicity but induced insufficient antitumor response in these high-tumor-burden patients. Remarkable antitumor activity by means of objective radiologic response or tumor marker decline was observed in 9 of 11 evaluable patients. For advanced-stage patients, a treatment activity of 100 kBq/kg of Ac-PSMA-617 per cycle repeated every 8 wk presents a reasonable trade-off between toxicity and biochemical response.
本研究旨在为前列腺特异性膜抗原（PSMA）阳性肿瘤表型的晚期转移性去势抵抗性前列腺癌患者制定 Ac-PSMA-617α放射治疗方案。根据从连续获得的 Lu-PSMA-617 扫描中得出的时间-活性曲线，假设不稳定子核素瞬时衰减，计算出剂量估计值。回顾性评估了经验性使用 50（=4）、100（=4）、150（=2）和 200 kBq/kg（=4）Ac-PSMA-617 的挽救疗法的毒性和治疗反应。14 名患者中有 8 名在 2 个月或 4 个月的间隔内接受了相同或降低剂量的进一步治疗。假设 Ac-PSMA-617 的相对生物学效应为 5，对于 1 MBq 的 Ac-PSMA-617 的剂量估计值显示，唾液腺的平均剂量为 2.3 Sv，肾脏为 0.7 Sv，红骨髓为 0.05 Sv，分别由 99.4%α、0.5%β和 0.1%光子辐射组成。在临床应用中，如果治疗活性超过每个周期 100 kBq/kg，则严重的口干症成为剂量限制毒性。在 100 kBq/kg 时，前列腺特异性抗原下降的持续时间不到 4 个月，但如果每 2 个月重复治疗，患者会经历附加的抗肿瘤作用。在这些高肿瘤负荷患者中，50 kBq/kg 的治疗活性没有毒性，但诱导的抗肿瘤反应不足。11 名可评估患者中有 9 名观察到明显的抗肿瘤活性，表现为客观影像学反应或肿瘤标志物下降。对于晚期患者，每个周期 100 kBq/kg 的 Ac-PSMA-617 活性，每 8 周重复一次，是毒性和生化反应之间的合理权衡。
