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Imaging tumor angiogenesis in breast cancer experimental lung metastasis with positron emission tomography, near-infrared fluorescence, and bioluminescence

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An Erratum to this article was published on 16 May 2013

Abstract

The goal of this study was to develop a molecular imaging agent that can allow for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of CD105 expression in metastatic breast cancer. TRC105, a chimeric anti-CD105 monoclonal antibody, was labeled with both a NIRF dye (i.e., IRDye 800CW) and 64Cu to yield 64Cu-NOTA-TRC105-800CW. Flow cytometry analysis revealed no difference in CD105 binding affinity/specificity between TRC105 and NOTA-TRC105-800CW. Serial bioluminescence imaging (BLI) was carried out to non-invasively monitor the lung tumor burden in BALB/c mice, after intravenous injection of firefly luciferase-transfected 4T1 (i.e., fLuc-4T1) murine breast cancer cells to establish the experimental lung metastasis model. Serial PET imaging revealed that fLuc-4T1 lung tumor uptake of 64Cu-NOTA-TRC105-800CW was 11.9 ± 1.2, 13.9 ± 3.9, and 13.4 ± 2.1 %ID/g at 4, 24, and 48 h post-injection respectively (n = 3). Biodistribution studies, blocking fLuc-4T1 lung tumor uptake with excess TRC105, control experiments with 64Cu-NOTA-cetuximab-800CW (which served as an isotype-matched control), ex vivo BLI/PET/NIRF imaging, autoradiography, and histology all confirmed CD105 specificity of 64Cu-NOTA-TRC105-800CW. Successful PET/NIRF imaging of tumor angiogenesis (i.e., CD105 expression) in the breast cancer experimental lung metastasis model warrants further investigation and clinical translation of dual-labeled TRC105-based agents, which can potentially enable early detection of small metastases and image-guided surgery for tumor removal.

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Acknowledgments

This work was supported, in part, by the University of Wisconsin Carbone Cancer Center, the Department of Defense (W81XWH-11-1-0644), and the Elsa U. Pardee Foundation. We thank Dr. Xiaoyuan Chen and Dr. Gang Niu for providing the fLuc-4T1 cells.

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Authors and Affiliations

  1. Department of Medical Physics, University of Wisconsin – Madison, Room 7137, 1111 Highland Avenue, Madison, WI, 53705, USA

    Yin Zhang, Hector F. Valdovinos, Todd E. Barnhart & Weibo Cai

  2. Department of Radiology, University of Wisconsin – Madison, Room 7137, 1111 Highland Avenue, Madison, WI, 53705, USA

    Hao Hong, Tapas R. Nayak, Duane V. Myklejord & Weibo Cai

  3. TRACON Pharmaceuticals, Inc., San Diego, CA, USA

    Charles P. Theuer

  4. University of Wisconsin Carbone Cancer Center, Madison, WI, USA

    Weibo Cai

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  1. Yin Zhang
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  2. Hao Hong
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Correspondence to Weibo Cai.

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Zhang, Y., Hong, H., Nayak, T.R. et al. Imaging tumor angiogenesis in breast cancer experimental lung metastasis with positron emission tomography, near-infrared fluorescence, and bioluminescence. Angiogenesis 16, 663–674 (2013). https://doi.org/10.1007/s10456-013-9344-y

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  • DOI: https://doi.org/10.1007/s10456-013-9344-y

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