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Mol Pharm. 2012 Mar 5;9(3):645-53. doi: 10.1021/mp200592m. Epub 2012 Jan 31.

Positron emission tomography and optical imaging of tumor CD105 expression with a dual-labeled monoclonal antibody.

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1
Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, United States.

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.

PMID:
22292418
PMCID:
PMC3295892
DOI:
10.1021/mp200592m
[Indexed for MEDLINE]
Free PMC Article
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