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

// Sara E.S. Lange 1 , Alex Zheleznyak 2 , Matthew Studer 1 , Daniel J. O’Shannessy 3 , Suzanne E. Lapi 2,4 and Brian A. Van Tine 1,4 1 Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO, USA 2 Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA 3 Translational Medicine and Diagnostics, Morphotek Inc., Exton, PA, USA 4 Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA Correspondence to: Brian A. Van Tine, email: // Keywords : 89Zr, Ontuxizumab, sarcoma, TEM-1, immuno-PET Received : November 27, 2015 Accepted : January 25, 2016 Published : February 21, 2016 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 89 Zr-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 89 Zr and evaluated for immunoreactivity preservation. 89 Zr-Ontuxizumab was injected into mice with high or null expressing TEM-1 xenografts. In vivo PET imaging experiments were performed. Conclusion: 89 Zr-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.