Targeted Alpha Therapy of mCRPC with 225Actinium-PSMA-617: Dosimetry estimate and empirical dose finding
Targeted Alpha Therapy of mCRPC with 225Actinium-PSMA-617: Dosimetry estimate and empirical dose finding
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使用 225Actinium-PSMA-617 进行 mCRPC 的靶向 Alpha 治疗：剂量测定估计和经验剂量发现
DOI：
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Morgenstern Alfred
中科院分区：
文献类型：
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作者：
Kratochwil Clemens;B. Frank;Rathke Hendrik;Bronzel Marcus;Apostolidis Christos;Weichert Wilko;Haberkorn Uwe;Giesel Frederik;Morgenstern Alfred
制定针对具有 PSMA 阳性肿瘤表型的晚期转移性去势抵抗性前列腺癌患者的 225Ac-PSMA-617 α 放射治疗方案。方法：假设不稳定子体核素立即衰变，根据连续进行的 177Lu-PSMA-617 扫描推断出 225Ac 的物理半衰期，计算剂量测定估计值。根据经验使用 50kBq/kg (n=4)、100kBq/kg (n=4)、150kBq/kg (n=2)、200kBq/kg (n=4) 225AcPSMA-617 进行挽救治疗，回顾性评估毒性和治疗反应。 14 名患者中有 8 名以 2 或 4 个月的间隔接受了进一步的周期，其中的活动量相同或逐渐降低。结果：假设相对生物有效性为 5，对 1 MBq 225Ac-PSMA-617 的剂量测定估计显示，唾液腺平均剂量为 2.3 Sv，肾脏平均剂量为 0.7 Sv，红骨髓平均剂量为 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，如果每个周期的治疗活性超过100kBq/kg，严重的口干症就会成为剂量限制性毒性。在 100kBq/kg 剂量下，PSA 下降持续时间<4 个月，但如果每 2 个月重复治疗一次，患者会经历额外的抗肿瘤作用。 50kBq/kg 的治疗活动没有毒性，但在这些高肿瘤负荷患者中诱导的抗肿瘤反应不足。在 9/11 可评估患者中观察到通过客观放射学反应或肿瘤标志物下降而具有显着的抗肿瘤活性。结论：对于晚期患者，每周期 100kBq/kg 225Ac-PSMA-617 每 8 周重复一次的治疗活动在毒性和生化反应之间呈现出合理的权衡。
To develop a treatment protocol for 225Ac-PSMA-617 alpha-radiation therapy in advanced stage, metastatic castration-resistant prostate cancer patients with PSMA-positive tumor phenotype. Methods: A dosimetry estimate was calculated based on time-activity-curves derived from serially performed 177Lu-PSMA-617 scans extrapolated to the physical half-life of 225Ac, assuming instant decay of instable daughter nuclides. Salvage therapies empirically conducted with 50kBq/kg (n=4), 100kBq/kg (n=4), 150kBq/kg (n=2), 200kBq/kg (n=4) 225AcPSMA-617 were evaluated retrospectively regarding toxicity and treatment response. 8 out of 14 patients received further cycles in either 2 or 4 months intervals with identical or de-escalated activities. Results: Dosimetry estimates for 1 MBq of 225Ac-PSMA-617 assuming a relative biological 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% alpha, 0.5% beta and 0.1% photon radiation, respectively. In clinical application, severe xerostomia became the dose-limiting toxicity if treatment activity exceeded 100kBq/kg per cycle. At 100kBq/kg duration of PSA-decline was <4 months, but if therapy was repeated every 2 months patients experienced additive anti-tumor effects. Treatment activities of 50kBq/kg were without toxicity but induced insufficient anti-tumor response in these high tumor burden patients. Remarkable anti-tumor activity by means of objective radiological response or tumor marker decline was observed in 9/11 evaluable patients. Conclusion: For advanced stage patients a treatment activity of 100kBq/kg 225Ac-PSMA-617 per cycle repeated every 8 weeks presents a reasonable trade-off between toxicity and biochemical response.
[68Ga]Ga-PSMA-HBED-CC 的新临床前和放射性药物方面：一种用于前列腺癌成像的新 PET 示踪剂。
DOI：
10.3390/ph7070779
发表时间：
2014-06-30
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
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作者：
Eder M;Neels O;Müller M;Bauder-Wüst U;Remde Y;Schäfer M;Hennrich U;Eisenhut M;Afshar-Oromieh A;Haberkorn U;Kopka K
通讯作者：
Kopka K
实体瘤放射免疫治疗中的高线性能量转移 (LET) α 与低 LET β 发射体：213Bi 与 90Y 标记的 CO17-1A Fab 片段在人类结肠癌模型中的治疗功效和剂量限制毒性。
DOI：
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发表时间：
1999
期刊：
Cancer research.
影响因子：
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作者：
Behr,TM;Behe,M;Stabin,MG;Wehrmann,E;Apostolidis,C;Molinet,R;Strutz,F;Fayyazi,A;Wieland,E;Gratz,S;Koch,L;Goldenberg,DM;Becker,W
通讯作者：
Becker,W
影响因子：
9.3
作者：
Benesova, Martina;Schaefer, Martin;Eder, Matthias
通讯作者：
Eder, Matthias