title: 177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy.
abstract: 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.
authors.affiliation: Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, Bad Berka, Germany; and richard.baum@zentralklinik.de.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Baum
authors.affiliation: Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, Bad Berka, Germany; and.
authors.forename: Harshad R
authors.initials: HR
authors.lastname: Kulkarni
authors.affiliation: Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, Bad Berka, Germany; and.
authors.forename: Christiane
authors.initials: C
authors.lastname: Schuchardt
authors.affiliation: Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, Bad Berka, Germany; and.
authors.forename: Aviral
authors.initials: A
authors.lastname: Singh
authors.affiliation: Pharmaceutical Radiochemistry, Faculties of Chemistry and Medicine, Technical University Munich, Munich, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Wirtz
authors.affiliation: Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, Bad Berka, Germany; and.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiessalla
authors.affiliation: Pharmaceutical Radiochemistry, Faculties of Chemistry and Medicine, Technical University Munich, Munich, Germany.
authors.forename: Margret
authors.initials: M
authors.lastname: Schottelius
authors.affiliation: Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, Bad Berka, Germany; and.
authors.forename: Dirk
authors.initials: D
authors.lastname: Mueller
authors.affiliation: Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, Bad Berka, Germany; and.
authors.forename: Ingo
authors.initials: I
authors.lastname: Klette
authors.affiliation: Pharmaceutical Radiochemistry, Faculties of Chemistry and Medicine, Technical University Munich, Munich, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
mesh_terms: D000368:Aged; D000954:Antigens, Surface / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D004151:Dipeptides / Q000627:therapeutic use; D018572:Disease-Free Survival; D004492:Edetic Acid / Q000031:analogs & derivatives; D004906:Erythrocyte Count; D005709:Gallium Isotopes; D005710:Gallium Radioisotopes; D043425:Glutamate Carboxypeptidase II / Q000009:adverse effects / Q000627:therapeutic use*; D006573:Heterocyclic Compounds, 1-Ring / Q000627:therapeutic use; D006801:Humans; D007958:Leukocyte Count; D008187:Lutetium; D008297:Male; D009362:Neoplasm Metastasis; D009842:Oligopeptides; D009942:Organometallic Compounds / Q000627:therapeutic use; D010146:Pain / Q000209:etiology / Q000532:radiotherapy; D018579:Patient Selection; D049268:Positron-Emission Tomography; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C000610110:Pluvicto; D000954:Antigens, Surface; D004151:Dipeptides; D005709:Gallium Isotopes; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D009842:Oligopeptides; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C000718244:gallium 68 PSMA-11; D008187:Lutetium; D004492:Edetic Acid; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen
keywords: PSMA; radioligand therapy; theranostics