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  2. Multimodal Investigation of Angiogenesis and Its Prevention by Small Compounds in a Zebrafish Cancer Model

Multimodal Investigation of Angiogenesis and Its Prevention by Small Compounds in a Zebrafish Cancer Model

  • Adv Sci (Weinh). 2025 Jun 25:e15176. doi: 10.1002/advs.202415176.
Marco Andreana 1 Ryan Sentosa 1 Caterina Sturtzel 2 3 Martin Pfister 1 René Werkmeister 1 Anna Schmitt 4 5 David Traver 5 Rainer Leitgeb 1 Wolfgang Drexler 1 Martin Distel 2 3 6 Angelika Unterhuber 1
Affiliations

Affiliations

  • 1 Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, 1090, Austria.
  • 2 Innovative Cancer Models, St. Anna Children's Cancer Research Institute, Vienna, 1090, Austria.
  • 3 Zebrafish Platform Austria for preclinical drug screening (ZANDR), Vienna, 1090, Austria.
  • 4 Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University Cologne, 50935, Cologne, Germany.
  • 5 Department of Cell and Developmental Biology, University of California San Diego, La Jolla, 92093, USA.
  • 6 Division of Pediatric Hematology and Oncology, Intermountain Primary Children's Hospital, Huntsman Cancer Institute, Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, 84113, USA.
Abstract

Aberrant angiogenesis is a hallmark of many pathologies. In Cancer, tumor growth and metastasis strongly depend on angiogenesis triggered by neoplastic cells. Antiangiogenic therapies are approved to treat different kinds of Cancer. However, the success of these treatments is so far limited as some patients do not respond at all and Others develop resistances. Thus, a deeper understanding of the mechanisms driving tumor angiogenesis and the variations in tumor vessels is crucial. Optical coherence tomography angiography (OCTA) is a fast volumetric imaging technique that provides detailed insights into tumor vascularization and perfusion of vessels in a label-free and non-invasive manner. An ultra-high resolution OCTA and confocal fluorescence imaging pipeline are developed to analyze tumor vascularization and blood perfusion in vivo, using a zebrafish Cancer model. OCTA imaging operating at 800 nm is optimized to show slow blood flow allowing to compare the functionality of blood vessels in healthy and tumor-bearing zebrafish. Furthermore, effects of small compounds on tumor vascularization can be investigated with our setup. The key outcomes include a qualitative assessment of vascularization and blood vessel perfusion, along with a quantitative analysis of vessel structure, to evaluate how effective the drugs were at different concentrations.

Keywords

angiographic imaging; cancer model; in vivo; label‐free; optical coherence tomography; optical coherence tomography angiography; topological descriptors.

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