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2-NBDG Fluorescence Imaging of Hypermetabolic Circulating Tumor Cells in Mouse Xenograft model of Breast Cancer

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Abstract

Objectives

To determine use of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG) as a tracer for detection of hypermetabolic circulating tumor cells (CTC) by fluorescence imaging.

Procedures

Human breast cancer cells were implanted in the mammary gland fat pad of athymic mice to establish orthotopic human breast cancer xenografts as a mouse model of circulating breast cancer cells. Near-infrared fluorescence imaging of the tumor-bearing mice injected with 2-DeoxyGlucosone 750 (2-DG 750) was conducted to assess glucose metabolism of xenograft tumors. Following incubation with fluorescent 2-NBDG, circulating breast cancer cells in the blood samples collected from the tumor-bearing mice were collected by magnetic separation, followed by fluorescence imaging for 2-NBDG uptake by circulating breast cancer cells, and correlation of the number of hypermetabolic circulating breast cancer cells with tumor size at the time when the blood samples were collected.

Results

Human breast cancer xenograft tumors derived from MDA-MB-231, BT474, or SKBR-3 cells were visualized on near-infrared fluorescence imaging of the tumor-bearing mice injected with 2-DG 750. Hypermetabolic circulating breast cancer cells with increased uptake of fluorescent 2-NBDG were detected in the blood samples from tumor-bearing mice and visualized by fluorescence imaging, but not in the blood samples from normal control mice. The number of hypermetabolic circulating breast cancer cells increased along with growth of xenograft tumors, with the number of hypermetabolic circulating breast cancer cells detected in the mice bearing MDA-MB231 xenografts larger than those in the mice bearing BT474 or SKBR-3 xenograft tumors.

Conclusions

Circulating breast cancer cells with increased uptake of fluorescent 2-NBDG were detected in mice bearing human breast cancer xenograft tumors by fluorescence imaging, suggesting clinical use of 2-NBDG as a tracer for fluorescence imaging of hypermetabolic circulating breast cancer cells.

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Acknowledgments

This study was supported by a grant from the Department of Defense CDMRP BCRP (W81XWH1110188) to F.P., and a faculty research start-up grant to F. P. from the Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, Texas, USA. Imaging infrastructure is provided by Southwestern Small Animal Imaging Research Program supported in part by U24 CA126608 and Simmons Cancer Center (P30 CA142543).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Radiology, University of Texas Southwestern Medical Center, The Clements Imaging Building, NE3.240, 5323 Harry Hines Blvd, Dallas, TX, 75390-8542, USA

    Huawei Cai & Fangyu Peng

  2. Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Fangyu Peng

  3. Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Fangyu Peng

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  1. Huawei Cai
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  2. Fangyu Peng
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Correspondence to Fangyu Peng.

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Cai, H., Peng, F. 2-NBDG Fluorescence Imaging of Hypermetabolic Circulating Tumor Cells in Mouse Xenograft model of Breast Cancer. J Fluoresc 23, 213–220 (2013). https://doi.org/10.1007/s10895-012-1136-z

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  • DOI: https://doi.org/10.1007/s10895-012-1136-z

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