title: PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617.
abstract: Prostate-specific membrane antigen (PSMA) is an excellent target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). Besides high affinity and long tumor retention, the DOTA-conjugated ligand PSMA-617 has low kidney uptake, making it an excellent choice for therapeutic application. We retrospectively report our experience with (177)Lu-PSMA-617-targeted radionuclide therapy in a case series of mCRPC patients resistant to other treatments.
  
  
  METHODS
  Patients with PSMA-positive tumor phenotypes were selected by molecular imaging. Thirty patients received 1-3 cycles of (177)Lu-PSMA-617. During therapy, pharmacokinetics and radiation dosimetry were evaluated. Blood cell count was checked every 2 wk after the first and every 4 wk after succeeding cycles. Prostate-specific antigen (PSA) was determined every 4 wk. Radiologic restaging was performed after 3 cycles.
  
  
  RESULTS
  Twenty-one of 30 patients had a PSA response; in 13 of 30 the PSA decreased more than 50%. After 3 cycles, 8 of 11 patients achieved a sustained PSA response (>50%) for over 24 wk, which also correlated with radiologic response (decreased lesion number and size). Normally, acute hematotoxicity was mild. Diffuse bone marrow involvement was a risk factor for higher grade myelosuppression but could be identified by PSMA imaging in advance. Xerostomia, nausea, and fatigue occurred sporadically (<10%). Clearance of non-tumor-bound tracer was predominantly renal and widely completed by 48 h. Safety dosimetry revealed kidney doses of approximately 0.75 Gy/GBq, red marrow doses of 0.03 Gy/GBq, and salivary gland doses of 1.4 Gy/GBq, irrespective of tumor burden and consistent on subsequent cycles. Mean tumor-absorbed dose ranged from 6 to 22 Gy/GBq during cycle 1.
  
  
  CONCLUSIONS
  (177)Lu-PSMA-617 is a promising new option for therapy of mCRPC and deserves more attention in larger prospective trials.
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: Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (dkfz), Heidelberg, Germany.
authors.forename: Frederik L
authors.initials: FL
authors.lastname: Giesel
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Melsa
authors.initials: M
authors.lastname: Stefanova
authors.affiliation: Division of Radiopharmaceutical Chemistry, German Cancer Research Center (dkfz), Heidelberg, Germany; and.
authors.forename: Martina
authors.initials: M
authors.lastname: Benešová
authors.affiliation: ABX-CRO, Dresden, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bronzel
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (dkfz), Heidelberg, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Afshar-Oromieh
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
authors.affiliation: Division of Radiopharmaceutical Chemistry, German Cancer Research Center (dkfz), Heidelberg, Germany; and.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.affiliation: Division of Radiopharmaceutical Chemistry, German Cancer Research Center (dkfz), Heidelberg, Germany; and.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kopka
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (dkfz), Heidelberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood*; D004151:Dipeptides / Q000493:pharmacokinetics*; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000493:pharmacokinetics*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D004151:Dipeptides; D006573:Heterocyclic Compounds, 1-Ring; C000602389:PSMA-617; D019275:Radiopharmaceuticals; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen
keywords: 177Lu; PSMA; castration-resistant prostate cancer; dosimetry; pharmacokinetics; radionuclide therapy