Threshold Analysis and Biodistribution of Fluorescently Labeled Bevacizumab in Human Breast Cancer
Koch M, De Jong JS, Glatz J, Symvoulidis P, Lamberts LE, Adams ALL, Kranendonk MEG, Van Scheltinga AGTT, Aichler M, Jansen L, De Vries J, Lub-De Hooge MN, Schroder CP, Jorritsma-Smit A, Linssen MD, De Boer E, Van Der Vegt B, Nagengast WB, Elias SG, Oliveira S, Witkamp AJ, Mali WPTM, Van Der Wall E, Garcia-Allende PB, Van Diest PJ, De Vries EGE, Walch A, Van Dam GM, Ntziachristos V (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 77
Pages Range: 623-631
Journal Issue: 3
DOI: 10.1158/0008-5472.CAN-16-1773
Abstract
In vivo tumor labeling with fluorescent agents may assist endoscopic and surgical guidance for cancer therapy as well as create opportunities to directly observe cancer biology in patients. However, malignant and nonmalignant tissues are usually distinguished on fluorescence images by applying empirically determined fluorescence intensity thresholds. Here, we report the development of fSTREAM, a set of analytic methods designed to streamline the analysis of surgically excised breast tissues by collecting and statistically processing hybrid multiscale fluorescence, color, and histology readouts toward precision fluorescence imaging. fSTREAM addresses core questions of how to relate fluorescence intensity to tumor tissue and how to quantitatively assign a normalized threshold that sufficiently differentiates tumor tissue from healthy tissue. Using fSTREAM we assessed human breast tumors stained in vivo with fluorescent bevacizumab at microdose levels. Showing that detection of such levels is achievable, we validated fSTREAM for high-resolution mapping of the spatial pattern of labeled antibody and its relation to the underlying cancer pathophysiology and tumor border on a per patient basis. We demonstrated a 98% sensitivity and 79% specificity when using labeled bevacizumab to outline the tumor mass. Overall, our results illustrate a quantitative approach to relate fluorescence signals to malignant tissues and improve the theranostic application of fluorescence molecular imaging.
Involved external institutions
Technische Universität München (TUM)
Germany (DE)
University Medical Centre Utrecht (UMC Utrecht)
Netherlands (NL)
University of Groningen / Rijksuniversiteit Groningen
Netherlands (NL)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Universiteit Utrecht (UU) / Utrecht University
Netherlands (NL)
Germany (DE)
University Medical Centre Utrecht (UMC Utrecht)
Netherlands (NL)
University of Groningen / Rijksuniversiteit Groningen
Netherlands (NL)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Universiteit Utrecht (UU) / Utrecht University
Netherlands (NL)
How to cite
APA:
Koch, M., De Jong, J.S., Glatz, J., Symvoulidis, P., Lamberts, L.E., Adams, A.L.L.,... Ntziachristos, V. (2017). Threshold Analysis and Biodistribution of Fluorescently Labeled Bevacizumab in Human Breast Cancer. Cancer Research, 77(3), 623-631. https://doi.org/10.1158/0008-5472.CAN-16-1773
MLA:
Koch, Maximilian, et al. "Threshold Analysis and Biodistribution of Fluorescently Labeled Bevacizumab in Human Breast Cancer." Cancer Research 77.3 (2017): 623-631.
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