title: Pharmacokinetics and PET imaging properties of two recombinant anti-PSMA antibody fragments in comparison to their parental antibody.
abstract: BACKGROUND
  Radioimmunoimaging with disease-specific tracers can be advantageous compared to that with nonspecific tracers for the imaging of glucose metabolism and cell proliferation. Monoclonal antibodies (mAbs) or their fragments are excellent tools for immuno-positron emission tomography (PET). In this study, PSMA-specific mAb 3/F11 and its recombinant fragments were compared for the imaging of prostate cancer in xenografts.
  
  
  METHODS
  Recombinant anti-PSMA antibody fragments D7-Fc and D7-CH3 were constructed by genetically fusing the binding domains of mAb 3/F11 (D7) to the human IgG3 CH3 or CH2-CH3 (Fc) domain. The fragments and the mAb 3/F11 were DOTA conjugated, tested in vitro, and radiolabeled with (64) Cu. PSMA-positive C4-2 and PSMA-negative DU 145 prostate cancer xenografts were used for PET-MR imaging and for ex vivo biodistribution.
  
  
  RESULTS
  The constructs showed strong and specific binding to PSMA-positive C4-2 cells in vitro which did not decrease after DOTA conjugation. Both tested fragments showed stable accumulation in PSMA-positive C4-2 tumors at all measured time points but reduced uptake compared to the full-length antibody. Other organs and PSMA-negative tumors showed a very low tracer uptake only 3 hr after injection, with the exception of the kidneys, which demonstrated high radioactivity uptake due to rapid renal clearance of the mAb fragments.
  
  
  CONCLUSIONS
  Stable tumor uptake and fast serum clearance of the tested radiolabeled fragments was observed in this preclinical study compared to the full length mAb. Since the fragments show rapid and specific tumor uptake, the tested fragments might serve as tools for theranostic imaging with suitable isotopes for radioimmunotherapy.
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University, Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiehr
authors.forename: Patrick
authors.initials: P
authors.lastname: Bühler
authors.forename: Dorothee
authors.initials: D
authors.lastname: Gierschner
authors.forename: Philipp
authors.initials: P
authors.lastname: Wolf
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Rolle
authors.forename: Christian
authors.initials: C
authors.lastname: Kesenheimer
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.forename: Ursula
authors.initials: U
authors.lastname: Elsässer-Beile
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology*; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments
keywords: PSMA; antibody; fragment; immuno-PET; prostate cancer