title: High-resolution animal PET imaging of prostate cancer xenografts with three different 64Cu-labeled antibodies against native cell-adherent PSMA.
abstract: BACKGROUND
  The prostate specific membrane antigen (PSMA) is expressed by virtually all prostate cancers and represents an ideal target for diagnostic and therapeutic strategies. This article compares the in vivo behavior and tumor uptake of three different radiolabeled anti-PSMA monoclonal antibodies (mAbs) and corresponding F(ab)(2) and Fab fragments thereof.
  
  
  METHODS
  The mAbs 3/A12, 3/F11, and 3/E7 and fragments of 3/A12 were conjugated with the chelating agent DOTA and radiolabeled with 64Cu. For the microPET imaging studies, SCID mice bearing PSMA-positive C4-2 and PSMA-negative DU 145 prostate cancer xenografts were used. Each animal received 20-30 microg radiolabeled mAb or fragment corresponding to an activity of 8-14 MBq. Imaging was performed 3, 24, and 48 hr post-injection. After the last scan, mice were sacrificed and tracer in vivo biodistribution was measured by gamma-counting.
  
  
  RESULTS
  Static microPET images of mice with PSMA-positive tumors revealed a high uptake of the mAbs in the C4-2 tumors at 24 and 48 hr after tracer injection and only a minimal distribution in the DU 145 tumors and other organs. In contrast, the F(ab)(2) and Fab fragments of 3/A12 were detected at a high extend in the kidney but not in the C4-2 tumors. These results were confirmed by gamma counting of dissected organs after the final imaging.
  
  
  CONCLUSIONS
  Due to the high and specific uptake of the 64Cu-labeled mAbs in PSMA-positive tumors, these antibodies represent excellent tools for prostate cancer imaging.
authors.affiliation: Department of Urology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Alt
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiehr
authors.forename: Walter
authors.initials: W
authors.lastname: Ehrlichmann
authors.forename: Gerald
authors.initials: G
authors.lastname: Reischl
authors.forename: Philipp
authors.initials: P
authors.lastname: Wolf
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.forename: Ursula
authors.initials: U
authors.lastname: Elsässer-Beile
authors.forename: Patrick
authors.initials: P
authors.lastname: Bühler
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D045744:Cell Line, Tumor; D004306:Dose-Response Relationship, Immunologic; D043425:Glutamate Carboxypeptidase II / Q000276:immunology*; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D011467:Prostate / Q000276:immunology; D014018:Tissue Distribution / Q000276:immunology; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II