NIH Research Festival
Sentinel lymph node biopsy (SLNB) has emerged as the preferred standard procedure in patients with breast cancer, melanoma and other types of cancer. Herein, we developed a method to intra-operatively map the SLNs and differentiate tumor metastases within SLNs at the same time, with the aim to provide more accurate and real-time intraoperative guidance. Hyaluronic acid (HA), a ligand of LYVE-1, is employed as a SLN mapping agent after being conjugated with Cy5.5. Different sized HAs (5K, 10 and 20K) were tested in normal mice and mice with localized inflammation to optimize LN retention time and signal to background ratio. Cetuximab, an antibody against epidermal growth factor receptor (EGFR), was labeled with IRDye800 for detecting metastatic tumors. Tumor metastasized LN model was developed by hock injection of Fluc-22B cells and the metastases were confirmed by bioluminescence imaging (BLI). IRDye800-Cetuximab was intravenously administered 24 h before local administration of Cy5.5-HA. Binding of HA with LYVE-1 was confirmed by ELISA and fluorescence staining. HA with a size of 10K was chosen based on the favorable migration and retention profile. After sequential administration of IRD 800-cetuximab intravenously and Cy5.5-HA locally to a mouse model with LN tumor metastases and fluorescence optical imaging, partially metastasized LNs were successfully distinguished from un-metastasized LNs and fully tumor occupied LNs, based on the different signal patterns. Convenient combination of lymphatic mapping agents and tumor targeting agents can provide accurate and real-time intra-operative guidance to spare the time spent waiting for a biopsy result.
Scientific Focus Area: Cancer Biology
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