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

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• 作者：Yin Zhang ; Hao Hong ; Jonathan W. Engle ; Yunan Yang ; Charles P. Theuer ; Todd E. Barnhart ; Weibo Cai
• 刊名：Molecular Pharmaceutics
• 出版年：2012
• 出版时间：March 5, 2012
• 年：2012
• 卷：9
• 期：3
• 页码：645-653
• 全文大小：477K
• 年卷期：v.9,no.3(March 5, 2012)
• ISSN：1543-8392

文摘

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 ⁶⁴Cu to yield ⁶⁴Cu-NOTA鈥揟RC105鈥?00CW. Flow cytometry analysis revealed no difference in CD105 binding affinity/specificity between TRC105 and NOTA鈥揟RC105鈥?00CW. Serial PET imaging revealed that the 4T1 murine breast tumor uptake of ⁶⁴Cu-NOTA鈥揟RC105鈥?00CW was 5.2 卤 2.7, 11.0 卤 1.4, and 13.0 卤 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 ⁶⁴Cu-NOTA鈥揟RC105鈥?00CW. Successful PET/NIRF imaging of CD105 expression warrants further investigation and clinical translation of dual-labeled TRC105-based imaging agents.

Keywords:

CD105/endoglin; positron emission tomography (PET); near-infrared fluorescence (NIRF); tumor angiogenesis; TRC105; ⁶⁴Cu; breast cancer