Journal article
Multimodality Imaging of Breast Cancer Experimental Lung Metastasis with Bioluminescence and a Monoclonal Antibody Dual-Labeled with 89Zr and IRDye 800CW
Department of Radiology, University of Wisconsin - Madison, WI, USA1
Department of Medical Physics, University of Wisconsin - Madison, WI, USA2
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA3
TRACON Pharmaceuticals, Inc., San Diego, CA, USA4
University of Wisconsin Carbone Cancer Center, Madison, WI, USA5
Metastatic breast cancer is incurable. The goal of this study was to develop a positron emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging of CD105 expression in breast cancer experimental lung metastasis. TRC105, a chimeric anti-CD105 antibody, was dual-labeled with a NIRF dye (IRDye 800CW) and 89Zr to yield 89Zr-Df-TRC105-800CW.
Luciferase-transfected 4T1 murine breast cancer cells were injected intravenously into female mice to establish the tumor model. Bioluminescence imaging (BLI) was carried out to non-invasively monitor the lung tumor burden. PET imaging revealed that 4T1 lung tumor uptake of 89Zr-Df-TRC105-800CW was 8.7±1.4, 10.9±0.5, and 9.7±1.1 %ID/g at 4, 24, and 48 h post-injection (n = 4), with excellent tumor contrast.
Biodistribution studies, blocking, control studies with 89Zr-Df-cetuximab-800CW, ex vivo BLI/PET/NIRF imaging, and histology all confirmed CD105 specificity of the tracer. Broad clinical potential of TRC105-based agents was shown in many tumor types, which also enabled early detection of small metastasis and intraoperative guidance for tumor removal.
Language: | Undetermined |
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Publisher: | American Chemical Society (ACS) |
Year: | 2014 |
Pages: | 2339-2349 |
ISSN: | 15438392 and 15438384 |
Types: | Journal article |
DOI: | 10.1021/mp300277f |
89Zr Animals Benzenesulfonates Breast Neoplasms Breast cancer CD105 (endoglin) Cell Line, Tumor Female Flow Cytometry Human Umbilical Vein Endothelial Cells Humans IRDye 800CW Indoles Lung Neoplasms Mice Mice, Inbred BALB C Zirconium lung metastasis near-infrared fluorescence (NIRF) positron emission tomography (PET) tumor angiogenesis