title: 225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer.
abstract: Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide-labeled PSMA ligand. Although the case series is still ongoing, we here report in advance about two patients in highly challenging clinical situations who showed a complete response to225Ac-PSMA-617 therapy.
  
  
  METHODS
  68Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq activity of225Ac-PSMA-617 per kilogram of body weight was administered bimonthly. Prostate-specific antigen response and hematologic toxicity were measured at least every 4 wk. Restaging was performed with68Ga-PSMA-11 PET/CT.
  
  
  RESULTS
  Both patients experienced a prostate-specific antigen decline to below the measurable level and showed a complete response on imaging. No relevant hematologic toxicity was observed. Xerostomia was the only mentionable clinical side effect.
  
  
  CONCLUSIONS
  Targeted α-therapy with225Ac-PSMA-617, although still experimental, obviously has strong potential to significantly benefit advanced-stage prostate cancer patients.
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany clemens.kratochwil@med.uni-heidelberg.de.
authors.forename: Clemens
authors.initials: C
authors.lastname: Kratochwil
authors.affiliation: European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Bruchertseifer
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Frederik L
authors.initials: FL
authors.lastname: Giesel
authors.affiliation: European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Weis
authors.affiliation: Department of Nuclear Medicine, RWTH University Hospital Aachen, Aachen, Germany; and.
authors.forename: Frederik A
authors.initials: FA
authors.lastname: Verburg
authors.affiliation: Department of Nuclear Medicine, RWTH University Hospital Aachen, Aachen, Germany; and.
authors.forename: Felix
authors.initials: F
authors.lastname: Mottaghy
authors.affiliation: Division of Radiopharmaceutical Chemistry, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kopka
authors.affiliation: European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany.
authors.forename: Christos
authors.initials: C
authors.lastname: Apostolidis
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
authors.affiliation: European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Morgenstern
mesh_terms: D000186:Actinium; D000512:Alpha Particles / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000378:metabolism*; D001610:Beta Particles / Q000627:therapeutic use; D004151:Dipeptides / Q000627:therapeutic use*; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000627:therapeutic use*; D006801:Humans; D008187:Lutetium / Q000627:therapeutic use; D008297:Male; D009362:Neoplasm Metastasis; D000072078:Positron Emission Tomography Computed Tomography; D017430:Prostate-Specific Antigen; D064129:Prostatic Neoplasms, Castration-Resistant / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D011868:Radioisotopes / Q000627:therapeutic use*
chemical_list: D000954:Antigens, Surface; D004151:Dipeptides; D006573:Heterocyclic Compounds, 1-Ring; C000602389:PSMA-617; D011868:Radioisotopes; D008187:Lutetium; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen; D000186:Actinium
keywords: 225Ac; PSMA; alpha-therapy