title: Imaging of prostate cancer with immuno-PET and immuno-SPECT using a radiolabeled anti-EGP-1 monoclonal antibody.
abstract: hRS7 is a humanized IgG1 monoclonal antibody directed against the epithelial glycoprotein-1 (EGP-1; also known as TROP2). This antigen is found in many epithelial cancers, including prostate cancer, and therefore this antibody could be suitable for targeting this cancer. In this study, the characteristics of hRS7 for targeting prostate cancer were examined. The potential for immuno-PET with (89)Zr-hRS7 and immuno-SPECT with (111)In-hRS7 was assessed using nude mice with human prostate cancer xenografts.
  
  
  METHODS
  EGP-1 expression was assessed by immunohistology in human primary and metastatic prostate cancer samples and in PC3 xenografts. The optimal antibody protein dose for prostate cancer targeting was examined in nude mice with subcutaneous PC3 xenografts, and then the biodistribution of (111)In-, (125)I-, and (89)Zr-labeled hRS7 was determined in subcutaneous PC3 xenografts at 1, 3, and 7 d after injection. Immuno-PET and immuno-SPECT were performed with (89)Zr-hRS7 and (111)In-hRS7 in mice with subcutaneous and intraprostatic PC3 xenografts, respectively.
  
  
  RESULTS
  Immunohistochemical analysis showed abundant EGP-1 expression in human primary and metastatic prostate cancers and in PC3 xenografts. (111)In-hRS7 and (89)Zr-hRS7 preferentially and specifically accumulated in PC3 xenografts, with tumor uptake as high as 60% injected dose per gram at a protein dose of 0.1 μg per mouse. PC3 tumors in nude mice were clearly visualized with both tracers with immuno-PET and immuno-SPECT.
  
  
  CONCLUSIONS
  hRS7 shows excellent in vivo tumor targeting in human prostate cancer xenografts. Therefore, hRS7 is a potential vehicle for targeting prostate cancer.
authors.affiliation: Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. k.vanrij@akf.umcn.nl
authors.forename: Catharina M
authors.initials: CM
authors.lastname: van Rij
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sharkey
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: Cathelijne
authors.initials: C
authors.lastname: Frielink
authors.forename: Janneke D M
authors.initials: JD
authors.lastname: Molkenboer
authors.forename: Gerben M
authors.initials: GM
authors.lastname: Franssen
authors.forename: Wietske M
authors.initials: WM
authors.lastname: van Weerden
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007205:Indium Radioisotopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014183:Transplantation, Heterologous; D015040:Zirconium
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D007205:Indium Radioisotopes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C499380:TACSTD2 protein, human; D015040:Zirconium