Generation and Characterization of Novel Pan-Cancer Anti-uPAR Fluorescent Nanobodies as Tools for Image-Guided Surgery
- Łukasz Mateusiak 1, Sam Floru 1, Timo W M De Groof 1, Janne Wouters 1, Noemi B Declerck 1, Pieterjan Debie 1, Simone Janssen 1,2, Katty Zeven 1, Janik Puttemans 1, Cécile Vincke 3,4, Karine Breckpot 5, Nick Devoogdt 1, Sophie Hernot 1
- 1Laboratory for Molecular Imaging and Therapy, Vrije Universiteit Brussel (VUB), MITH, Laarbeeklaan 103, Brussels, 1090, Belgium.
- 2Faculty of Veterinary Medicine, Small Animal Department, Ghent University (UGent), Salisburylaan 133, Merelbeke, 9820, Belgium.
- 3Laboratory for Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Pleinlaan 2, Brussels, 1050, Belgium.
- 4Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Pleinlaan 2, Brussels, 1050, Belgium.
- 5Laboratory for Molecular and Cellular Therapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, Brussels, 1090, Belgium.
- 0Laboratory for Molecular Imaging and Therapy, Vrije Universiteit Brussel (VUB), MITH, Laarbeeklaan 103, Brussels, 1090, Belgium.
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View abstract on PubMed
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.
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