title: Development, optimization, and validation of novel anti-TEM1/CD248 affinity agent for optical imaging in cancer.
abstract: Tumor Endothelial Marker-1 (TEM1/CD248) is a tumor vascular marker with high therapeutic and diagnostic potentials. Immuno-imaging with TEM1-specific antibodies can help to detect cancerous lesions, monitor tumor responses, and select patients that are most likely to benefit from TEM1-targeted therapies. In particular, near infrared(NIR) optical imaging with biomarker-specific antibodies can provide real-time, tomographic information without exposing the subjects to radioactivity. To maximize the theranostic potential of TEM1, we developed a panel of all human, multivalent Fc-fusion proteins based on a previously identified single chain antibody (scFv78) that recognizes both human and mouse TEM1. By characterizing avidity, stability, and pharmacokinectics, we identified one fusion protein, 78Fc, with desirable characteristics for immuno-imaging applications. The biodistribution of radiolabeled 78Fc showed that this antibody had minimal binding to normal organs, which have low expression of TEM1. Next, we developed a 78Fc-based tracer and tested its performance in different TEM1-expressing mouse models. The NIR imaging and tomography results suggest that the 78Fc-NIR tracer performs well in distinguishing mouse- or human-TEM1 expressing tumor grafts from normal organs and control grafts in vivo. From these results we conclude that further development and optimization of 78Fc as a TEM1-targeted imaging agent for use in clinical settings is warranted.
authors: Ovarian Cancer Research Center, University of Pennsylvania; These authors contributed equally to this work.
authors: Chunsheng
authors: C
authors: Li
authors: Ovarian Cancer Research Center, University of Pennsylvania; Department of Immunology, Norman Bethune College of Medicine Jilin University; These authors contributed equally to this work.
authors: Junying
authors: J
authors: Wang
authors: Ovarian Cancer Research Center, University of Pennsylvania.
authors: Jia
authors: J
authors: Hu
authors: Department of Cancer Biology, University of Pennsylvania.
authors: Yi
authors: Y
authors: Feng
authors: Saitama International Medical Center Saitama Medical University.
authors: Kosei
authors: K
authors: Hasegawa
authors: Ovarian Cancer Research Center, University of Pennsylvania.
authors: Xiaohui
authors: X
authors: Peng
authors: Ovarian Cancer Research Center, University of Pennsylvania.
authors: Xingmei
authors: X
authors: Duan
authors: Ovarian Cancer Research Center, University of Pennsylvania.
authors: Aizhi
authors: A
authors: Zhao
authors: Nuclear Medicine & Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania.
authors: John L
authors: JL
authors: Mikitsh
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania.
authors: Vladimir R
authors: VR
authors: Muzykantov
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania; Nuclear Medicine & Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania.
authors: Ann-Marie
authors: AM
authors: Chacko
authors: Nuclear Medicine & Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania.
authors: Daniel A
authors: DA
authors: Pryma
authors: Ludwig Cancer Research Center, University of Lausanne.
authors: Steven M
authors: SM
authors: Dunn
authors: Ovarian Cancer Research Center, University of Pennsylvania; Ludwig Cancer Research Center, University of Lausanne.
authors: George
authors: G
authors: Coukos
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000737:chemistry* / Q000276:immunology; D061848:Optical Imaging; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C078203:CD248 protein, human; D007128:Immunoglobulin Fragments; D011993:Recombinant Fusion Proteins