Abstract
The accurate detection of lymph node metastases is essential for treatment success in early-stage malignant cancer. Sentinel lymph node (SLN) biopsy is the most effective procedure for detecting small or micrometastases that are undetectable by conventional imaging modalities. To demonstrate a new approach for developing a more efficient SLN biopsy procedure, we reported a two-stage imaging method combining lymphoscintigraphy and near-infrared (NIR) fluorescence imaging to depict metastatic cancer cells in SLNs in vivo. Furthermore, the theranostic potential of the combined procedure was examined by cell culture and xenograft mouse model. Anti-HER2 and anti-epidermal growth factor receptor (EGFR) affibody probes were used for NIR fluorescence imaging. Strong NIR fluorescence signal intensity of the anti-EGFR affibody probe was observed in SAS cells (EGFR positive). Radioactivity in the SLNs was clearly observed in the in vivo studies. High anti-EGFR affibody NIR fluorescence intensity was observed in the metastatic lymph nodes in mice. The addition of the IR700-conjugated anti-EGFR affibody to the culture medium decreased the proliferation of SAS cells. Decreased proliferation was shown in Ki-67 immunohistochemistry in xenograft tumors. Our data suggest that a two-stage combined imaging method using lymphoscintigraphy and affibody probes may offer the direct visualization of metastatic lymph nodes as an easily applied technique in SLN biopsy. Although further animal studies are required to assess the effect of treating lymphatic metastasis in this approach, our study results provide a foundation for the further development of this promising imaging and treatment strategy for earlier lymph node metastasis detection and treatment.
Highlights
Lymph node staging is a significant prognostic factor in many malignancies, especially solid malignant tumors
To verify the NIR imaging efficacy of the anti-epidermal growth factor receptor (EGFR) affibody probe, the anti-EGFR affibody probe was added to the conditioned medium of SAS cells or MCF-7 cells
Strong NIR fluorescence from the anti-EGFR affibody probe was observed in the SAS cells in contrast to the negative signal observed from the MCF-7 cells
Summary
Lymph node staging is a significant prognostic factor in many malignancies, especially solid malignant tumors. The accurate detection of lymph node metastases is essential for treatment success in early-stage malignant cancer. Sentinel lymph node (SLN) biopsy is the most effective procedure for detecting small or micrometastases that are undetectable by conventional imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET). SLNs are the first nodes in the regional lymph basin to direct drain lymph from primary lesions. Histopathological examination of one or a few SLNs can reveal the stage of the regional lymph drainage field. SLN biopsy has been a standard procedure in breast cancer and melanoma and has since been introduced in head and neck cancer and other malignancies [1,2,3,4]. Patients with a negative SLN biopsy are spared unnecessary extensive surgery, thereby reducing the risk of postsurgical complications, such as lymphedema and numbness, while those with a positive SLN biopsy undergo the lymph node dissection surgery at an early stage
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