[161Tb]Tb-PSMA-617 RLT在mCRPC患者常规PSMA RLT后的前瞻性注册试验经验

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-08-16 eCollection Date: 2025-01-01 DOI:10.7150/thno.115831
Florian Rosar, Caroline Burgard, Christine Petrescu, Arne Blickle, Mark Bartholomä, Stephan Maus, Moritz B Bastian, Tilman Speicher, Andrea Schaefer-Schuler, Samer Ezziddin
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引用次数: 0

摘要

理由:放射性核素161Tb是一个越来越被讨论的潜在候选放射配体治疗(RLT)。通过大量低能俄钻和转换电子的发射,161Tb比常用的177Lu具有物理优势,从而产生更高的局部吸收剂量。在这项研究中,我们介绍了初始PSMA RLT后不同临床环境下的[161Tb]Tb-PSMA-617 RLT的初步经验。方法:该研究纳入了n=18例转移性去雄抵抗性前列腺癌(mCRPC)患者,参与前瞻性登记(NCT04833517),并在初始PSMA RLT后接受[161Tb]Tb-PSMA-617治疗。总共47个周期的[161Tb]Tb-PSMA-617 RLT治疗,每位患者中位数为3个周期(1 - 4个周期)。每周期161Tb的平均给药活性为6.2±0.8 GBq,平均累积活性为16.1±4.9 GBq。结果通过生化和分子成像反应、无进展生存期(PFS)和总生存期(OS)来评估。不良事件采用“不良事件通用术语标准”(CTCAE v.5.0)分级系统进行评估。结果:在先前使用[177Lu]Lu-PSMA-617或甚至在225Ac增强后RLT后反应不足或进展的患者的异质队列中,生化和分子成像反应率分别为38.9%和44.4%,中位PFS和OS分别为3.5和11.3个月。在最初对[177Lu]Lu-PSMA-617 RLT有反应的患者中观察到最佳反应和结果。大多数治疗后记录的不良事件为轻度或中度(CTCAE°1或°2);较高级别(CTCAE°3或°4)少见(血小板减少2例,贫血4例,肾功能损害4例)。没有因治疗相关不良事件而中断治疗的记录。结论:这些试点结果证实了161Tb是一种有希望的PSMA RLT放射性核素,并且表明[161Tb]Tb-PSMA-617即使在包括标准PSMA RLT在内的多线全身治疗后的晚期mCRPC环境中,也是一种潜在的有效和安全的治疗选择。有必要进行更大规模的研究来证实和扩展这一初步经验,甚至在早期CRPC环境下的临床试验也很有希望,这是基于我们对PSMA RLT中这种基于放射性核素的新颖性的初步印象。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Pilot experience of [<sup>161</sup>Tb]Tb-PSMA-617 RLT in mCRPC patients after conventional PSMA RLT within a prospective registry.

Pilot experience of [<sup>161</sup>Tb]Tb-PSMA-617 RLT in mCRPC patients after conventional PSMA RLT within a prospective registry.

Pilot experience of [<sup>161</sup>Tb]Tb-PSMA-617 RLT in mCRPC patients after conventional PSMA RLT within a prospective registry.

Pilot experience of [161Tb]Tb-PSMA-617 RLT in mCRPC patients after conventional PSMA RLT within a prospective registry.

Rationale: The radionuclide 161Tb is an increasingly discussed potential candidate for radioligand therapy (RLT). Through the considerable emitted amount of low-energy Auger and conversion electrons, 161Tb offers physical advantages over the commonly used 177Lu, resulting in higher locally absorbed doses. In this study, we present initial experience with [161Tb]Tb-PSMA-617 RLT across different clinical settings following initial PSMA RLT. Methods: The study involved n=18 patients with metastasized castration-resistant prostate cancer (mCRPC) participating in a prospective registry (NCT04833517) and receiving [161Tb]Tb-PSMA-617 after initial PSMA RLT with established radionuclides (177Lu, 225Ac). In total 47 cycles of [161Tb]Tb-PSMA-617 RLT were administered with a median of 3 cycles (1 - 4 cycles) per patient. The mean administered activity of 161Tb per cycle was 6.2 ± 0.8 GBq, the mean cumulative activity was 16.1 ± 4.9 GBq. Outcome was evaluated by biochemical and molecular imaging response, progression-free survival (PFS), and overall survival (OS). Adverse events were assessed by 'Common Terminology Criteria for Adverse Events' (CTCAE v.5.0) grading system. Results: In the heterogeneous cohort of patients previously experiencing insufficient response or progression post RLT with [177Lu]Lu-PSMA-617, or even after 225Ac augmentation, biochemical and molecular imaging response rates were 38.9% and 44.4%, median PFS and OS 3.5 and 11.3 months, respectively. The best response and outcome were observed in patients who initially responded to [177Lu]Lu-PSMA-617 RLT. The majority of all post therapeutically recorded adverse events were mild or moderate (CTCAE °1 or °2); higher grades (CTCAE °3 or °4) were rarely observed (2 cases of thrombocytopenia, 4 cases of anemia and 4 cases of renal impairment). No treatment discontinuation due to therapy related adverse events was recorded. Conclusion: These pilot results confirm 161Tb as a promising radionuclide for PSMA RLT and suggest [161Tb]Tb-PSMA-617 as a potential effective and safe treatment option even in the advanced mCRPC setting after multi-line systemic therapies including standard PSMA RLT. Larger studies are warranted to confirm and extend this initial experience and clinical trials even in earlier CRPC settings appear promising based on our initial impression of this radionuclide-based novelty in PSMA RLT.

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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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