Development of 89Zr-Ontuxizumab for in vivo TEM-1/endosialin PET applications.

Academic Article

Abstract

  • PURPOSE: 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. EXPERIMENTAL DESIGN: 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. CONCLUSION: 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.
  • Published In

  • Oncotarget  Journal
  • Keywords

  • 89Zr, Ontuxizumab, TEM-1, immuno-PET, sarcoma, Animals, Antibodies, Monoclonal, Humanized, Antigens, CD, Antigens, Neoplasm, Biomarkers, Tumor, Cell Line, Tumor, Humans, Mice, Mice, Nude, Positron-Emission Tomography, Radioisotopes, Sarcoma, Xenograft Model Antitumor Assays, Zirconium
  • Digital Object Identifier (doi)

    Author List

  • Lange SES; Zheleznyak A; Studer M; O'Shannessy DJ; Lapi SE; Van Tine BA
  • Start Page

  • 13082
  • End Page

  • 13092
  • Volume

  • 7
  • Issue

  • 11