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- Title
Optical Imaging of Triple-Negative Breast Cancer Cells in Xenograft Athymic Mice Using an ICAM-1-Targeting Small-Molecule Probe.
- Authors
Zhang, Yanqiu; Wang, Mengru; Liu, Wanhua; Peng, Xin
- Abstract
<bold>Purpose: </bold>The development of early, accurate diagnostic strategies for triple-negative breast cancer (TNBC) remains a significant challenge. Intercellular adhesion molecule-1 (ICAM-1) overexpressed in human TNBC cells is a potential molecular target and biomarker for diagnosis. In this study, small-molecule probe (denoted as γ3-Cy5.5) constructed with a short 17-mer linear peptide (γ3) and near-infrared fluorescence (NIRF) dye cyanine 5.5 (Cy5.5) was used to detect the expression of ICAM-1 in vitro and in vivo, and to diagnose TNBC via NIRF imaging.<bold>Procedures: </bold>Western blotting and flow cytometric analysis were used for the detection of ICAM-1 expression in MDA-MB-231 and MCF-7 cells. The cytotoxicity of the small-molecule probe γ3-Cy5.5 was detected using the CCK8 assay. The in vitro targeting of the small-molecule probe γ3-Cy5.5 was verified via flow cytometry and a laser scanning confocal microscope. Finally, the targeting of small-molecule probe in vivo and ex vivo was observed by NIRF imaging.<bold>Results: </bold>Western blotting and flow cytometry demonstrate that ICAM-1 was highly expressed in the MDA-MB-231 TNBC cell line. Laser confocal microscopy and flow cytometry results show that TNBC cells have an increased cellular uptake of γ3-Cy5.5 compared to the control probe γ3S-Cy5.5. With in vivo NIRF, a significantly higher Cy5.5 signal appeared in the tumors of mice administered γ3-Cy5.5 than those treated with γ3S-Cy5.5. The target-to-background ratio observed on the NIRF images was significantly higher in the γ3-Cy5.5 group (10.2, 13.6) compared with the γ3S-Cy5.5 group (4.4, 4.0) at 1 and 2 h, respectively.<bold>Conclusions: </bold>This is the first report of the use of ICAM-1-specific small-molecule probe for in vivo NIRF optical imaging of TNBC. This method provides a noninvasive and specific strategy for the early diagnosis of TNBC.
- Subjects
TRIPLE-negative breast cancer; CANCER cells; OPTICAL images; BREAST imaging; CELL adhesion; HYDROCARBON metabolism; MOLECULAR probes; RESEARCH; ANIMAL experimentation; RESEARCH methodology; EVALUATION research; DIAGNOSTIC imaging; COMPARATIVE studies; RESEARCH funding; CELL lines; BREAST tumors; ANTIGENS; MICE
- Publication
Molecular Imaging & Biology, 2019, Vol 21, Issue 5, p835
- ISSN
1536-1632
- Publication type
journal article
- DOI
10.1007/s11307-018-01312-3