Rosar Florian, Krause Jonas, Bartholomä Mark, Maus Stephan, Stemler Tobias, Hierlmeier Ina, Linxweiler Johannes, Ezziddin Samer, Khreish Fadi
Department of Nuclear Medicine, Saarland University, 66421 Homburg, Germany.
Department of Urology, Saarland University, 66421 Homburg, Germany.
Pharmaceutics. 2021 May 14;13(5):722. doi: 10.3390/pharmaceutics13050722.
The use of Ac in prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), either as monotherapy or in combination with Lu, is a promising therapy approach in patients with metastatic castration-resistant prostate carcinoma (mCRPC). In this study, we report the efficacy and safety of [Ac]Ac-PSMA-617 augmented [Lu]Lu-PSMA-617 RLT in Lu-naive mCRPC patients ( = 15) with poor prognosis (presence of visceral metastases, high total tumor burden with diffuse bone metastases or a short PSA doubling time of <2 months). Biochemical (by PSA serum value) and molecular imaging response (by [Ga]Ga-PSMA-11 PET/CT) was assessed after two cycles of [Lu]Lu-PSMA-617 RLT, with at least one [Ac]Ac-PSMA-617 augmentation. In addition, PSA-based progression-free survival (PSA-PFS), overall survival (OS) and toxicity (according to CTCAE) were analyzed. We observed a biochemical- and molecular imaging-based partial remission in 53.3% (8/15) and 66.7% (10/15) of patients, respectively. The median PSA-PFS and OS was 9.1 and 14.8 months, respectively. No serious acute adverse events were recorded. Two out of fifteen patients experienced grade 3 anemia. No other grade 3/4 toxicities were observed. RLT-related xerostomia (grade 1/2) was recorded in 2/15 patients. Our data showed a high clinical efficacy with a favorable side effects profile of [Ac]Ac-PSMA-617 augmented [Lu]Lu-PSMA-617 RLT in this highly challenging patient cohort.
锕（Ac）在前列腺特异性膜抗原（PSMA）靶向放射性配体疗法（RLT）中，无论是作为单一疗法还是与镥（Lu）联合使用，对于转移性去势抵抗性前列腺癌（mCRPC）患者而言都是一种很有前景的治疗方法。在本研究中，我们报告了[锕-225]Ac-PSMA-617增强[镥-177]Lu-PSMA-617 RLT在初治的预后较差（存在内脏转移、伴有弥漫性骨转移的高肿瘤总负荷或前列腺特异性抗原（PSA）加倍时间短于2个月）的mCRPC患者（n = 15）中的疗效和安全性。在进行两个周期的[镥-177]Lu-PSMA-617 RLT且至少有一次[锕-225]Ac-PSMA-617增强后，评估生化反应（通过PSA血清值）和分子影像反应（通过[镓-68]Ga-PSMA-11 PET/CT）。此外，还分析了基于PSA的无进展生存期（PSA-PFS）、总生存期（OS）和毒性（根据美国国立癌症研究所不良事件通用术语标准（CTCAE））。我们分别观察到53.3%（8/15）和66.7%（10/15）的患者出现基于生化和分子影像的部分缓解。PSA-PFS和OS的中位数分别为9.1个月和14.8个月。未记录到严重的急性不良事件。15名患者中有2名出现3级贫血。未观察到其他3/4级毒性反应。15名患者中有2名记录到与RLT相关的口干（1/2级）。我们的数据显示，在这个极具挑战性的患者队列中，[锕-225]Ac-PSMA-617增强[镥-177]Lu-PSMA-617 RLT具有高临床疗效且副作用特征良好。
