Baum Richard P, Kulkarni Harshad R, Schuchardt Christiane, Singh Aviral, Wirtz Martina, Wiessalla Stefan, Schottelius Margret, Mueller Dirk, Klette Ingo, Wester Hans-Jürgen
Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, Bad Berka, Germany; and
Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, Bad Berka, Germany; and.
J Nucl Med. 2016 Jul;57(7):1006-13. doi: 10.2967/jnumed.115.168443. Epub 2016 Jan 21.
The objective of this study was to analyze the safety and efficacy of the (177)Lu-labeled DOTAGA-based prostate-specific membrane antigen (PSMA) ligand (177)Lu-DOTAGA-(I-y)fk(Sub-KuE) ((177)Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC).
Fifty-six mCRPC patients underwent PSMA radioligand therapy (RLT) with (177)Lu-PSMA. (68)Ga-PSMA-(N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid) ((68)Ga-PSMA) PET/CT was used for patient selection and follow-up after PSMA RLT. Hematologic status, renal function, and serum prostate-specific antigen levels were documented before and after therapy. Dosimetry was performed in 30 patients.
(177)Lu-PSMA demonstrated high absorbed tumor doses (median, 3.3 mGy/MBq) compared with the levels in normal organs. Parotid glands received higher doses (1.3 mGy/MBq) than kidneys (0.8 mGy/MBq). All patients tolerated the therapy without any acute adverse effects. Except for mild reversible xerostomia in 2 patients, no long-term side effects were observed. There was a small but statistically significant reduction in erythrocyte and leukocyte counts; only the reduction in erythrocyte counts decreased slightly below the reference range. No thrombocytopenia occurred. The severity of pain was significantly reduced in 2 of 6 patients (33.3%). A decrease in prostate-specific antigen levels was noted in 45 of 56 patients (80.4%). Of 25 patients monitored for at least 6 mo after 2 or more PSMA RLT cycles, a molecular response evaluation ((68)Ga-PSMA PET/CT) revealed partial remission in 14, stable disease in 2, and progressive disease in 9 patients. Contrast-enhanced CT revealed partial remission in 5, stable disease in 13, and progressive disease in 7 patients. The median progression-free survival was 13.7 mo, and the median overall survival was not reached during follow-up for 28 mo.
PSMA RLT with (177)Lu-PSMA is feasible, safe, and effective in end-stage progressive mCRPC with appropriate selection and follow-up of patients by (68)Ga-PSMA PET/CT through application of the concept of theranostics.
本研究的目的是分析¹⁷⁷Lu标记的基于DOTAGA的前列腺特异性膜抗原（PSMA）配体¹⁷⁷Lu-DOTAGA-(I-y)fk(Sub-KuE)（¹⁷⁷Lu-PSMA）在转移性去势抵抗性前列腺癌（mCRPC）患者中的安全性和有效性。
56例mCRPC患者接受了¹⁷⁷Lu-PSMA的PSMA放射性配体治疗（RLT）。⁶⁸Ga-PSMA-（N,N'-双-[2-羟基-5-（羧乙基）苄基]乙二胺-N,N'-二乙酸）（⁶⁸Ga-PSMA）PET/CT用于PSMA RLT后的患者选择和随访。记录治疗前后的血液学状态、肾功能和血清前列腺特异性抗原水平。对30例患者进行了剂量测定。
与正常器官中的水平相比，¹⁷⁷Lu-PSMA显示出较高的肿瘤吸收剂量（中位数，3.3 mGy/MBq）。腮腺接受的剂量（1.3 mGy/MBq）高于肾脏（0.8 mGy/MBq）。所有患者均耐受治疗，无任何急性不良反应。除2例患者出现轻度可逆性口干外，未观察到长期副作用。红细胞和白细胞计数有小幅但具有统计学意义的下降；只有红细胞计数的下降略低于参考范围。未发生血小板减少症。6例患者中有2例（33.3%）疼痛严重程度显著降低。56例患者中有45例（80.4%）前列腺特异性抗原水平下降。在25例接受2个或更多PSMA RLT周期后至少监测6个月的患者中，分子反应评估（⁶⁸Ga-PSMA PET/CT）显示14例部分缓解，2例病情稳定，9例病情进展。对比增强CT显示5例部分缓解，13例病情稳定，7例病情进展。无进展生存期的中位数为13.7个月，随访28个月期间总生存期的中位数未达到。
通过应用治疗诊断学概念，利用⁶⁸Ga-PSMA PET/CT对患者进行适当选择和随访，¹⁷⁷Lu-PSMA的PSMA RLT在晚期进展性mCRPC中是可行、安全且有效的。
