Positron Emission Tomography and Optical Imaging of Tumor CD105 Expression with a Dual-Labeled Monoclonal Antibody

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 Cu-64 to yield Cu-64-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 Cu-64-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 CD 105 specificity of Cu-64-NOTA-TRC105-800CW. Successful PET/NIRF imaging of CD105 expression warrants further investigation and clinical translation of dual-labeled TRC105-based imaging agents.