Gäble Alexander, Dierks Alexander, Rinscheid Andreas, Patt Marianne, Wienand Georgine, Pfob Christian H, Kircher Malte, Fukushima Kazuhito, Nikolić Ana Antić, Enke Johanna S, Janzen Tilman, Steinestel Julie, Kempter Hildegard, Trepel Martin, Weckermann Dorothea, Lapa Constantin, Bundschuh Ralph A
Nuclear Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
Bavarian Cancer Research Center (BZKF), Augsburg, Germany.
Eur J Nucl Med Mol Imaging. 2025 Feb;52(3):970-978. doi: 10.1007/s00259-024-06959-5. Epub 2024 Nov 4.
Radioligand therapy is an increasingly important option for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Radiohybrid ligands targeting prostate-specific membrane antigen (PSMA) are a novel group of theranostic radioligand therapy agents for which higher tumour absorbed radiation doses have been demonstrated compared to established PSMA ligands. Here, we report data from ten patients who were treated within a compassionate use program with the radiohybrid PSMA-ligand [Lu]Lu-rhPSMA-10.1 after experiencing disease progression under treatment with [Lu]Lu-PSMA-I&T.
Ten patients with advanced PSMA-positive prostate cancer who showed progression under treatment with [Lu]Lu-PSMA-I&T received up to three cycles of rescue therapy with [Lu]Lu-rhPSMA-10.1 (7.4-8.1 GBq per cycle). Efficacy (PSA response according to PCWG3 and RECIP) and overall survival were evaluated. Adverse events were recorded from first application.
Despite progression with [Lu]Lu-PSMA-I&T, after the first cycle of [Lu]Lu-rhPSMA-10.1 rescue therapy, five patients (50%) showed a decrease in serum PSA level. In imaging, three of the ten patients (30%) showed a partial radiologic response. Four of the five patients with a decrease of serum PSA under [Lu]Lu-rhPSMA-10.1 had initially responded to treatment with [Lu]Lu-PSMA-I&T but had become resistant. However, the remaining patient had shown continuous disease progression during [Lu]Lu-PSMA-I&T therapy but showed an immediate response to [Lu]Lu-rhPSMA-10.1. The additional treatment with [Lu]Lu-rhPSMA-10.1 was generally well tolerated by all patients.
Patients showing tumour progression while receiving [Lu]Lu-PSMA-I&T radioligand therapy may benefit from rescue therapy with the novel radiohybrid PSMA ligand, [Lu]Lu-rhPSMA-10.1. Higher tumour absorbed radiation doses with [Lu]Lu-rhPSMA-10.1 may overcome primary and acquired radiation resistance.
放射性配体疗法是治疗转移性去势抵抗性前列腺癌（mCRPC）日益重要的选择。靶向前列腺特异性膜抗原（PSMA）的放射性杂交配体是一类新型的治疗诊断放射性配体治疗剂，与已有的PSMA配体相比，其肿瘤吸收辐射剂量更高。在此，我们报告了10例患者的数据，这些患者在接受[Lu]Lu-PSMA-I&T治疗期间疾病进展后，在一项同情用药计划中接受了放射性杂交PSMA配体[Lu]Lu-rhPSMA-10.1的治疗。
10例PSMA阳性晚期前列腺癌患者在接受[Lu]Lu-PSMA-I&T治疗期间出现疾病进展，接受了最多三个周期的[Lu]Lu-rhPSMA-10.1挽救治疗（每个周期7.4 - 8.1 GBq）。评估疗效（根据PCWG3和RECIP标准的PSA反应）和总生存期。从首次应用开始记录不良事件。
尽管接受[Lu]Lu-PSMA-I&T治疗时疾病进展，但在[Lu]Lu-rhPSMA-10.1挽救治疗的第一个周期后，5例患者（50%）血清PSA水平下降。在影像学检查中，10例患者中有3例（30%）显示部分放射学反应。在[Lu]Lu-rhPSMA-10.1治疗下血清PSA下降的5例患者中，有4例最初对[Lu]Lu-PSMA-I&T治疗有反应，但后来产生了耐药性。然而，其余1例患者在[Lu]Lu-PSMA-I&T治疗期间疾病持续进展，但对[Lu]Lu-rhPSMA-10.1立即产生反应。所有患者对[Lu]Lu-rhPSMA-10.1的额外治疗耐受性普遍良好。
在接受[Lu]Lu-PSMA-I&T放射性配体治疗时出现肿瘤进展的患者可能从新型放射性杂交PSMA配体[Lu]Lu-rhPSMA-10.1的挽救治疗中获益。[Lu]Lu-rhPSMA-10.1更高的肿瘤吸收辐射剂量可能克服原发性和获得性辐射抗性。
