title: Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with131I-MIP-1095.
abstract: OBJECTIVE
  Prostate-specific membrane antigen (PSMA)-targeting radioligand therapy (RLT) was introduced in 2011. The first report described the antitumor and side effects of a single dose. The aim of this analysis was to evaluate toxicity and antitumor activity after single and repetitive therapies.
  
  
  METHODS
  Thirty-four men with metastatic castration-resistant prostate cancer received PSMA-RLT with131I-MIP-1095. Twenty-three patients received a second, and three patients a third dose, timed at PSA progression after an initial response to the preceding therapy. The applied doses were separated in three groups: <3.5, 3.5-5.0 and >5.0 GBq. Antitumor and side-effects were analyzed by blood samples and other clinical data. Follow-up was conducted for up to 5 years.
  
  
  RESULTS
  The best therapeutic effect was achieved by the first therapy. A PSA decline of ≥50% was achieved in 70.6% of the patients. The second and third therapies were significantly less effective. There was neither an association between the applied activity and PSA response or the time-to-progression. Hematologic toxicities were less prevalent but presented in a higher percentage of patients with increasing number of therapies. After hematologic toxicities, xerostomia was the second most frequent side effect and presented more often and with higher intensity after the second or third therapy.
  
  
  CONCLUSIONS
  The first dose of RLT with131I-MIP-1095 presented with low side effects and could significantly reduce the tumor burden in a majority of patients. The second and third therapies were less effective and presented with more frequent and more intense side effects, especially hematologic toxicities and xerostomia.
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany. a.afshar@gmx.de.|Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany. a.afshar@gmx.de.
authors.forename: Ali
authors.identifier: http://orcid.org/0000-0002-4492-4243
authors.initials: A
authors.lastname: Afshar-Oromieh
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany.|Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Zechmann
authors.affiliation: Progenics Pharmaceuticals, Inc., New York, NY, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Armor
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Spohn
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Debus
authors.affiliation: Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Holland-Letz
authors.affiliation: Division of Radiopharmaceutical Sciences, Department of Radiology, Weill Cornell Medicine, New York, NY, USA.|Citigroup Biomedical Imaging Center, Weill Cornell Medicine, New York, NY, 10021, USA.|Meyer Cancer Center, Weill Cornell Medicine, New York, NY, 10021, USA.
authors.forename: John
authors.initials: J
authors.lastname: Babich
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Kratochwil
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism*; D018450:Disease Progression; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D005971:Glutamates / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D008024:Ligands; D008297:Male; D009362:Neoplasm Metastasis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D012189:Retrospective Studies; D012449:Safety; D016019:Survival Analysis; D014508:Urea / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: C544834:2-(3-(1-carboxy-5-(3-(4-iodobphenyl)ureido)pentyl)ureido)pentanedioic acid; D000954:Antigens, Surface; D005971:Glutamates; D007457:Iodine Radioisotopes; D008024:Ligands; D014508:Urea; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: Endoradiotherapy; PSMA; Prostate cancer; Prostate-specific membrane antigen