title: Discrepancy Between Tumor Antigen Distribution and Radiolabeled Antibody Binding in a Nude Mouse Xenograft Model of Human Melanoma.
abstract: OBJECTIVE
  Biodistribution of antibodies is vital to successful immunoscintigraphy/immunotherapy, and it is assumed to be similar to antigen distribution. We measured and compared the binding pattern of radiolabeled antibody to tissue antigen distribution in a nude mouse xenograft model of human melanoma.
  
  
  METHODS
  We transplanted 107FEM-XII human melanoma cells into the right flank of five nude mice. For the control, we transplanted 5 × 106LS174T human colon cancer cells into the left flank. Two weeks later, 10 μCi of131I-labeled melanoma-associated 96.5 monoclonal antibody (targeting p97 antigen) was intravenously injected. Three days later, we sacrificed the mice and evaluated 96.5 antibody binding and concentration in the tumors by ex vivo quantitative autoradiography (QAR). Two months later, we incubated adjacent tumor tissue slices in various concentrations of125I-labeled 96.5 MoAb and evaluated the distribution/concentration of p97 antigen by in vitro QAR.
  
  
  RESULTS
  p97 antigen distribution was homogeneous in the tumors (total antigen concentration [Bmax] = 17.36-38.36 pmol/g). In contrast, radiolabeled 96.5 antibody binding was heterogenous between location within the tumor (estimated bound antigen concentration = 0.7-6.6 pmol/g). No quantifiable parameters were found to be related with radiolabeled antibody binding and tumor antigen distribution. Antibody-bound tumor antigen to total antigen ratios ranged between 2% and 38%.
  
  
  CONCLUSIONS
  Heterogeneous features of target antibody binding were observed in contrast to relatively homogenous feature of tumor antigen. We did not identify any correlations between p97 antigen distribution and 96.5 antibody binding in melanoma tissue. Radiolabeled 96.5 antibody binding patterns within melanoma cannot be predicted based on p97 antigen distribution in the tumor, which needs to be further studied with several other methods and more subjects in the future.
authors.affiliation: 1 Department of Nuclear Medicine, Seoul National University Hospital , Seoul, Korea.|2 Department of Nuclear Medicine, CHA Bundang Medical Center, CHA University , Seongnam, Korea.
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: 1 Department of Nuclear Medicine, Seoul National University Hospital , Seoul, Korea.
authors.forename: Jin Chul
authors.initials: JC
authors.lastname: Paeng
authors.affiliation: 1 Department of Nuclear Medicine, Seoul National University Hospital , Seoul, Korea.
authors.forename: Gi Jeong
authors.initials: GJ
authors.lastname: Cheon
authors.affiliation: 1 Department of Nuclear Medicine, Seoul National University Hospital , Seoul, Korea.|3 Cancer Research Institute, Seoul National University College of Medicine , Seoul, Korea.
authors.forename: Keon Wook
authors.initials: KW
authors.lastname: Kang
authors.affiliation: 1 Department of Nuclear Medicine, Seoul National University Hospital , Seoul, Korea.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.affiliation: 1 Department of Nuclear Medicine, Seoul National University Hospital , Seoul, Korea.|3 Cancer Research Institute, Seoul National University College of Medicine , Seoul, Korea.
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D006801:Humans; D000922:Immunotoxins / Q000276:immunology / Q000493:pharmacokinetics* / Q000494:pharmacology; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D008545:Melanoma / Q000276:immunology* / Q000532:radiotherapy; D058950:Melanoma-Specific Antigens / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D058950:Melanoma-Specific Antigens
keywords: I-131; antigen; melanoma; molecular imaging; monoclonal antibodies