177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy

被引:376
作者
Baum, Richard P. [1 ]
Kulkarni, Harshad R. [1 ]
Schuchardt, Christiane [1 ]
Singh, Aviral [1 ]
Wirtz, Martina [2 ,3 ]
Wiessalla, Stefan [1 ]
Schottelius, Margret [2 ,3 ]
Mueller, Dirk [1 ]
Klette, Ingo [1 ]
Wester, Hans-Juergen [2 ,3 ]
机构
[1] Zent Klin Bad Berka, Theranost Ctr Mol Radiotherapy & Mol Imaging, Robert Koch Allee 9, D-99437 Bad Berka, Germany
[2] Tech Univ Munich, Fac Chem, Pharmaceut Radiochem, Munich, Germany
[3] Tech Univ Munich, Fac Med, Munich, Germany
关键词
PSMA; radioligand therapy; theranostics; RADIONUCLIDE THERAPY; RADIATION-DOSIMETRY; PSMA INHIBITOR; PET/CT; GA-68; THERANOSTICS; SURVIVAL; PROBE;
D O I
10.2967/jnumed.115.168443
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
The objective of this study was to analyze the safety and efficacy of the Lu-177-labeled DOTAGA-based prostate-specific membrane antigen (PSMA) ligand Lu-177-DOTAGA-(l-y)fk(Sub-KuE) (Lu-177-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: Fifty-six mCRPC patients underwent PSMA radioligand therapy (RLT) with Lu-177-PSMA. Ga-68-PSMA-(N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid) (Ga-68-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. Results: Lu-177-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 (Ga-68-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. Conclusion: PSMA RLT with Lu-177-PSMA is feasible, safe, and effective in end-stage progressive mCRPC with appropriate selection and follow-up of patients by Ga-68-PSMA PET/CT through application of the concept of theranostics.
引用
收藏
页码:1006 / 1013
页数:8
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