title: Positron emission tomography and optical imaging of tumor CD105 expression with a dual-labeled monoclonal antibody.
abstract: CD105 (endoglin) is an independent prognostic marker for poor prognosis in >10 solid tumor types, including breast cancer. The goal of this study was to develop a CD105-specific agent for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging, which can have potential clinical applications in diagnosis and imaged-guided surgery of breast cancer. TRC105, a chimeric anti-CD105 monoclonal antibody, was labeled with both a NIRF dye (i.e., 800CW) and (64)Cu to yield (64)Cu-NOTA-TRC105-800CW. Flow cytometry analysis revealed no difference in CD105 binding affinity/specificity between TRC105 and NOTA-TRC105-800CW. Serial PET imaging revealed that the 4T1 murine breast tumor uptake of (64)Cu-NOTA-TRC105-800CW was 5.2 ± 2.7, 11.0 ± 1.4, and 13.0 ± 0.4% ID/g at 4, 24, and 48 h postinjection respectively. Tumor uptake as measured by ex vivo NIRF imaging exhibited a good linear correlation with the % ID/g values obtained from PET (R = 0.74). Biodistribution data were consistent with the PET/NIRF findings. Blocking experiments, control studies with dual-labeled cetuximab (an isotype-matched control antibody), and histology confirmed the CD105 specificity of (64)Cu-NOTA-TRC105-800CW. Successful PET/NIRF imaging of CD105 expression warrants further investigation and clinical translation of dual-labeled TRC105-based imaging agents.
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, United States.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Engle
authors.forename: Yunan
authors.initials: Y
authors.lastname: Yang
authors.forename: Charles P
authors.initials: CP
authors.lastname: Theuer
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism*; D045744:Cell Line, Tumor; D000071063:Endoglin; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D019265:Spectroscopy, Near-Infrared
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface