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Anti-mucin 4 fluorescent antibody brightly targets colon cancer in patient-derived orthotopic xenograft mouse models: A proof-of-concept study for future clinical applications

      Highlights

      • In this study, MUC4 was overexpressed in CRC primary and metastatic liver tumors compared to normal colon.
      • Anti-MUC4 antibodies conjugated to NIR dye can improve visualization of primary CRC.
      • Anti-MUC4 antibodies conjugated to NIR can also label CRLM in the liver bed.

      Abstract

      Background

      There is a high rate of positive surgical margins with resection of liver metastases in colorectal cancer (CRC). The present study reports using a fluorescent anti-mucin 4 (MUC4) antibodies to label primary CRC and liver metastases to better visualize tumor margins in mouse models.

      Methods

      Western blotting for MUC4 protein expression of normal colon and CRC tumor lysates was performed. Orthotopic primary and liver metastatic CRC mouse models received anti-MUC4 antibody conjugated to IR800 (MUC4-IR800). Mice were sacrificed and imaged after 48 hours.

      Results

      Western blotting demonstrated increased MUC4 expression in a human CRC cell line and patient-derived primary and liver-metastatic CRCs. The LS174T orthotopic primary CRC model tumor to background ratio (TBR) was 2.04 (±0.35). The patient-derived orthotopic xenograft (PDOX) primary CRC model TBR was 2.17 (±0.35). The PDOX liver metastasis model TBR was 1.56 (±0.53).

      Conclusion

      MUC4-IR800 provided bright labeling of primary and liver tumors in CRC orthotopic mouse models, demonstrating their future clinical potential for margin visualization in fluorescence guided surgery.

      Abbreviations:

      FGS (Fluorescence guided surgery), CRC (Colorectal cancer), MUC4 (Mucin 4), PDOX (Patient derived orthotopic xenograft), TBR (Tumor to background ratio), CRLM (Colorectal liver metastasis), ICG (Indocyanine green), PBS (Phosphate-buffered saline), SDS (sodium dodecyl sulfate), PBST (phosphate-buffered saline with tween 20), UC (Ulcerative colitis), HRP (horseradish peroxidase)
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