Matches in Ghent University Academic Bibliography for { <https://biblio.ugent.be/publication/01HTDSPMY4N9CECYWBSCEFJWNT> ?p ?o. }
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- 01HTDSPMY4N9CECYWBSCEFJWNT classification C3.
- 01HTDSPMY4N9CECYWBSCEFJWNT date "2023".
- 01HTDSPMY4N9CECYWBSCEFJWNT language "eng".
- 01HTDSPMY4N9CECYWBSCEFJWNT type conference.
- 01HTDSPMY4N9CECYWBSCEFJWNT subject "Medicine and Health Sciences".
- 01HTDSPMY4N9CECYWBSCEFJWNT presentedAt urn:uuid:284a1f22-1034-4028-96d2-d4fba0eba2e6.
- 01HTDSPMY4N9CECYWBSCEFJWNT abstract "Fluorescence molecular imaging plays an essential role in clinical applications such as image-guided surgery (IGS). This technology employs fluorescent contrast agents to specifically identify biomarkers expressed in diseased or healthy tissues. The urokinase plasminogen activator receptor (uPAR) is a molecular target that exhibits elevated expression in numerous human tumors. Targeting moieties such as single-domain antibodies (sdAbs), characterized by high target affinity and rapid systemic clearance, are excellent candidates for molecular imaging and offer significant advantages over small molecules, peptides, and antibodies. To address the need for a versatile tracer capable of detecting various cancer types, we have generated, developed, and preclinically validated a panel of anti-uPAR sdAbs with the intention of application in IGS.<br/>First, we demonstrate the capabilities of the generated sdAbs to bind uPAR on multiple types of cancer cells in vitro. Further, we present findings on the in vivo biodistribution of the sdAbs after radiolabeling (99mTc), corroborating specific tumor binding with high affinity in subcutaneous tumors of various origins in mice. Finally, we show the in vivo potential of the fluorescent sdAbs and their ability to distinguish between different types of cancers and healthy tissue by targeting uPAR on both tumor cells and tumor-associated stromal cells. To achieve this, we conjugated selected sdAbs with a novel near-infrared fluorescent dye (S775Z) and employed subcutaneous and orthotopic tumor models that closely mimic real-life clinical scenarios. <br/>Our findings extend to various cancer types, including glioblastoma, colorectal cancer, and pancreatic cancer metastasizing to the liver. We also demonstrate that elevated physiological uPAR expression in the spleen or liver does not impede the sdAbs’ ability to highlight cancer lesions in these organs. Notably, all the evaluated fluorescent conjugates accumulated specifically within the cancerous tissues, allowing for distinct visualization as early as one hour after intravenous administration. This prompt targeting resulted in relevant tumor-to-background ratios. <br/>In conclusion, the developed compounds exhibit translational potential for future clinical applications. For instance, they could be applied as contrast agents to non-invasively predict tumor aggressiveness or provide real-time guidance during surgical procedures. The developed sdAbs offer an attractive alternative to other compounds currently being investigated for IGS.".
- 01HTDSPMY4N9CECYWBSCEFJWNT author F5DA6C1A-B86A-11E8-8241-CD545707D3EF.
- 01HTDSPMY4N9CECYWBSCEFJWNT author urn:uuid:0f92b500-3b68-40e1-a024-972712062d18.
- 01HTDSPMY4N9CECYWBSCEFJWNT author urn:uuid:1ec0b604-bf91-4ca5-a633-368c193498fc.
- 01HTDSPMY4N9CECYWBSCEFJWNT author urn:uuid:350f0ba9-8df9-41fd-908f-dd947d6af145.
- 01HTDSPMY4N9CECYWBSCEFJWNT author urn:uuid:6a5f4724-7368-4c98-85ac-b1ac53c0e292.
- 01HTDSPMY4N9CECYWBSCEFJWNT author urn:uuid:73e50186-ef67-4304-a536-b66ac642ba00.
- 01HTDSPMY4N9CECYWBSCEFJWNT author urn:uuid:8f8b9f83-9bc9-4633-b9de-b8e415921ba1.
- 01HTDSPMY4N9CECYWBSCEFJWNT author urn:uuid:a2e4c91b-eb70-4a16-a492-51b025613e79.
- 01HTDSPMY4N9CECYWBSCEFJWNT author urn:uuid:c2314e77-1cd9-4e22-ac09-a0a584d410a1.
- 01HTDSPMY4N9CECYWBSCEFJWNT author urn:uuid:f56ea998-c588-4c02-b8be-fd4406610995.
- 01HTDSPMY4N9CECYWBSCEFJWNT dateCreated "2024-04-01T21:40:31Z".
- 01HTDSPMY4N9CECYWBSCEFJWNT dateModified "2024-07-09T15:31:24Z".
- 01HTDSPMY4N9CECYWBSCEFJWNT name "Novel uPAR-targeting fluorescent single-domain antibodies as tools for in vivo optical cancer imaging".
- 01HTDSPMY4N9CECYWBSCEFJWNT sameAs LU-01HTDSPMY4N9CECYWBSCEFJWNT.
- 01HTDSPMY4N9CECYWBSCEFJWNT sourceOrganization urn:uuid:1a4ff158-eaa5-4ef8-b3b9-4f30d8d8d554.
- 01HTDSPMY4N9CECYWBSCEFJWNT type C3.