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Tissue-simulating Phantoms for Assessing Potential Near-infrared Fluorescence Imaging Applications in Breast Cancer Surgery
Published on: September 19, 2014
A SLC7A5-Specific Near-Infrared Fluorescent Probe for Cancer-Targeted Imaging Applications
Wei Zhang1, Jialin Xu2, Liping Dong3
1Jiangsu Clinical Medicine Research Institute, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, P.R. China.
Abstract:
Extensive surgical resection improves survival in cancer patients. Fluorescence-guided imaging techniques have significantly enhanced the precision of cancer resections. Triple-negative breast cancer (TNBC) lacks expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), and no other targetable molecules have been identified. In this study, we verified that the L-type amino acid transporter 1 (LAT1, also known as SLC7A5) is overexpressed in triple-negative breast cancer (TNBC) cells and we constructed a novel near-infrared fluorescent dye Cys-PEG5-IR target to SLC7A5. We then report the SLC7A5 receptor specificity of Cys-PEG5-IR as a contrast agent for TNBC imaging in vitro and in vivo. The conjugation elevated cell fluorescence on SLC7A5-overexpressing TNBC cells and produced minimal cell fluorescence when treated with SLC7A5 knockdown. Tumor uptake of Cys-PEG5-IR was significantly higher than the unlabeled IR in the subcutaneous MDA-MB-231 TNBC xenograft. This work highlights the prospect of using methionine (Met) transport pathway as an alternative strategy for targeting cancer cells, especially TNBC cells.
Insights
Researchers developed a new near-infrared fluorescent dye targeting the SLC7A5 receptor for improved triple-negative breast cancer (TNBC) imaging. This dye enhances visualization of TNBC tumors, aiding surgical precision.
Area of Science:
- Biomedical Imaging
- Oncology
- Molecular Biology
Background:
- Surgical resection is crucial for cancer patient survival.
- Fluorescence-guided imaging improves cancer resection precision.
- Triple-negative breast cancer (TNBC) lacks specific molecular targets for therapy and imaging.
Purpose of the Study:
- To investigate L-type amino acid transporter 1 (LAT1/SLC7A5) as a target in TNBC.
- To develop and evaluate a novel near-infrared fluorescent dye (Cys-PEG5-IR) targeting SLC7A5 for TNBC imaging.
Main Methods:
- Verified SLC7A5 overexpression in TNBC cells.
- Synthesized Cys-PEG5-IR, a near-infrared fluorescent dye targeting SLC7A5.
- Assessed Cys-PEG5-IR specificity and efficacy in vitro (cell fluorescence) and in vivo (TNBC xenograft model).
Main Results:
- Cys-PEG5-IR showed enhanced fluorescence in SLC7A5-overexpressing TNBC cells.
- Fluorescence was minimal in cells with SLC7A5 knockdown.
- The dye exhibited significantly higher tumor uptake in a TNBC xenograft model compared to unlabeled dye.
Conclusions:
- SLC7A5 is a viable target for TNBC.
- Cys-PEG5-IR serves as an effective contrast agent for TNBC imaging.
- Targeting the methionine transport pathway offers a promising strategy for TNBC detection and treatment.
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