title: Current Status of Prostate-Specific Membrane Antigen Targeting in Nuclear Medicine: Clinical Translation of Chelator Containing Prostate-Specific Membrane Antigen Ligands Into Diagnostics and Therapy for Prostate Cancer.
abstract: The prostate-specific membrane antigen (PSMA) is expressed by approximately 90% of prostate carcinomas. The expression correlates with unfavorable prognostic factors, such as a high Gleason score, infiltrative growth, metastasis, and hormone-independence. The high specificity, especially in the undifferentiated stage, makes it an excellent target for diagnosis and therapy. Therefore, antibodies and small molecule inhibitors have been developed for imaging and therapy. In 2011 PSMA-11, a ligand that consists of the Glu-urea-motif and the chelator HBED-CC, which can be exclusively radiolabeled with (68)Ga for PET imaging, presented the clinical breakthrough for prostate cancer diagnostics. In two large diagnostic studies (n = 319 and n = 248) PET/CT with PSMA-11 successfully localized the recurrent tumor in approximately 90% of patients with biochemical relapse. Integrating PSMA-PET/CT into the planning phase of radiotherapy, the treatment concept is changed in 30%-50% of the patients. The combination of the Glu-urea-motif with DOTA, which can be labeled with several diagnostic and therapeutic radionuclides, opened new avenues for therapeutic usage of the small-molecule PSMA ligands. In the beginning of 2016, there are four confirmative reports (n = 19, n = 24, n = 30, and n = 56) from four different centers reporting a PSA response in approximately 70% of patients treated with (177)Lu-labeled PSMA ligands. In conclusion, the data available up to now indicate a widespread use of PSMA ligands for diagnostic applications with respect to staging, detection of recurrence, or metastases in patients with rising tumor markers and for therapy in case of failure of guideline-compliant treatment.
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
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 (E060), German Cancer Research Center (dkfz), Heidelberg, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Afshar-Oromieh
authors.affiliation: Division of Radiopharmaceutical Chemistry, German Cancer Research Center (dkfz), Heidelberg, Germany.
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 (E060), German Cancer Research Center (dkfz), Heidelberg, Germany. Electronic address: uwe.haberkorn@med.uni-heidelberg.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Frederik L
authors.initials: FL
authors.lastname: Giesel
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism*; D002614:Chelating Agents / Q000737:chemistry*; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods*; D009683:Nuclear Medicine / Q000379:methods*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000954:Antigens, Surface; D002614:Chelating Agents; D019275:Radiopharmaceuticals; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II