Generation and Characterization of Novel Pan-Cancer Anti-uPAR Fluorescent Nanobodies as Tools for Image-Guided Surgery

  • 0Laboratory for Molecular Imaging and Therapy, Vrije Universiteit Brussel (VUB), MITH, Laarbeeklaan 103, Brussels, 1090, Belgium.

Summary

This summary is machine-generated.

New fluorescent agents targeting urokinase plasminogen activator receptor (uPAR) show promise for cancer surgery. These anti-uPAR Nanobodies (Nbs) accurately detect tumors, potentially improving surgical precision and patient outcomes.

Area Of Science

  • Molecular imaging
  • Biomarker discovery
  • Nanotechnology in medicine

Background

  • Fluorescence molecular imaging is crucial for image-guided surgery.
  • Urokinase plasminogen activator receptor (uPAR) is a key biomarker overexpressed in various cancers.
  • Targeting uPAR can aid in tumor detection and delineation.

Purpose Of The Study

  • To generate and characterize anti-uPAR Nanobodies (Nbs) for fluorescence-guided surgery.
  • To evaluate the in vivo performance of fluorescently labeled anti-uPAR Nbs in preclinical tumor models.
  • To assess the potential of these agents in enhancing surgical tumor resection precision.

Main Methods

  • Llama immunization with human and murine uPAR protein to generate anti-uPAR Nbs.
  • In vitro characterization and in vivo testing of radiolabeled and fluorescently labeled Nbs.
  • Evaluation in subcutaneous and orthotopic tumor models, including a human glioma model.

Main Results

  • A panel of high-affinity anti-uPAR Nbs with specific binding to cancer cells was developed.
  • Fluorescently labeled Nbs demonstrated high tumor uptake and contrast in uPAR-expressing tumors.
  • Accurate tumor localization and demarcation were achieved in an orthotopic human glioma model.

Conclusions

  • Fluorescently labeled anti-uPAR Nbs are effective tools for molecular imaging in image-guided surgery.
  • These agents show potential for improving the precision of tumor resection.
  • Enhanced surgical precision could lead to improved patient survival rates.