2-NBDG fluorescence imaging of hypermetabolic circulating tumor cells in mouse xenograft model of breast cancer.

J Fluoresc. 2013 Jan;23(1):213-20.

Cai H, Peng F.

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

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.

PMID: 23054302

 

Supplement:

Malignant transformation of cells is associated with various metabolic changes. Based on increased tumor uptake of F-18 FDG radiotracer, a radiolabled glucose analogue, F-18 FDG positron emission tomography-computed tomograph (F-18 FDG PET/CT) is widely used for metabolic imaging of cancers. However, F-18 FDG PET/CT has low sensitivity for detection of small subcentimeter cancer lesions due to limited spatial resolution. 2-NBDG fluorescence imaging described in this article demonstrated usefulness of this fluorescent tracer for detection of hypermetabolic circulating breast cancer cells in xenograft model of breast cancer. 2-NBDG fluorescence imaging of CTCs holds potential as a new prognostic imaging test and could be used for longitudinal monitoring of cancer response to treatment in complementary with F-18 FDG PET/CT, considering simplicity and lower cost of 2-NBDG fluorescence imaging of CTCs compared with use of F-18 FDG PET/CT (Supplement Fig 1). 2-NBDG fluorescence imaging is expected to be useful for monitoring treatment response in the patients diagnosed with leukemia, particularly in children, when use of F-18 FDG PET/CT is limited. Furthermore, 2-NBDG fluorescence imaging of CTCs may be a useful test for metabolic imaging of cancer and monitoring cancer response to treatment when F-18 FDG PET or F-18 FDG PET/CT is not available.

Fangyu Peng-1

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