title: Development of 89Zr-Ontuxizumab for in vivo TEM-1/endosialin PET applications.
abstract: OBJECTIVE
  The complexity of sarcoma has led to the need for patient selection via in vivo biomarkers. Tumor endothelial marker-1 (TEM-1) is a cell surface marker expressed by the tumor microenvironment. Currently MORAb-004 (Ontuxizumab), an anti-TEM-1 humanized monoclonal antibody, is in sarcoma clinical trials. Development of positron emission tomography (PET) for in vivo TEM-1 expression may allow for stratification of patients, potentially enhancing clinical outcomes seen with Ontuxizumab.
  
  
  RESULTS
  Characterization of cell lines revealed clear differences in TEM-1 expression. One high expressing (RD-ES) and one low expressing (LUPI) cell line were xenografted, and mice were injected with 89Zr-Ontuxizumab. PET imaging post-injection revealed that TEM-1 was highly expressed and readily detectable in vivo only in RD-ES. In vivo biodistribution studies confirmed high radiopharmaceutical uptake in tumor relative to normal organs.
  
  
  METHODS
  Sarcoma cell lines were characterized for TEM-1 expression. Ontuxizumab was labeled with 89Zr and evaluated for immunoreactivity preservation. 89Zr-Ontuxizumab was injected into mice with high or null expressing TEM-1 xenografts. In vivo PET imaging experiments were performed.
  
  
  CONCLUSIONS
  89Zr-Ontuxizumab can be used in vivo to determine high versus low TEM-1 expression. Reliable PET imaging of TEM-1 in sarcoma patients may allow for identification of patients that will attain the greatest benefit from anti-TEM-1 therapy.
authors.affiliation: Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Sara E S
authors.initials: SE
authors.lastname: Lange
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Zheleznyak
authors.affiliation: Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Studer
authors.affiliation: Translational Medicine and Diagnostics, Morphotek Inc., Exton, PA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: O'Shannessy
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA.|Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Lapi
authors.affiliation: Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO, USA.|Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Van Tine
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes / Q000494:pharmacology*; D012509:Sarcoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D015040:Zirconium / Q000494:pharmacology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C078203:CD248 protein, human; D011868:Radioisotopes; C000604563:ontuxizumab; D015040:Zirconium
keywords: 89Zr; Ontuxizumab; TEM-1; immuno-PET; sarcoma