Koch, M. ; de Jong, J.S.* ; Glatz, J. ; Symvoulidis, P. ; Lamberts, L.E.* ; Adams, A.L.L.* ; Kranendonk, M.E.G.* ; Terwisscha van Scheltinga, A.G.* ; Aichler, M. ; Jansen, L.* ; de Vries, J.* ; Lub-de, Hoog, M.N.* ; Schröder, C.P.* ; Jorritsma-Smit, A.* ; Linssen, M.D.* ; de Boer, E.* ; van der Vegt, B.* ; Nagengast, W.B.* ; Elisas,S.G.* ; Oliveira, S.* ; Witkamp, A.J.* ; Mali, W.P.Th.M.* ; van der Wall, E.* ; Gracia-Allende, P.B. ; van Diest, P.J.* ; de Vries, E.G.* ; Walch, A.K. ; van Dam, G.M.* ; Ntziachristos, V.
Threshold analysis and biodistribution of fluorescently labeled bevacizumab in human breast cancer.
Cancer Res. 77, 623-631 (2017)
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 non-malignant 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 multi-scale 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 labelled 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.
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Publication type
Article: Journal article
Document type
Scientific Article
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Editors
Keywords
Indocyanine Green; Folate; Surgery; Margins; Safety; Agent; Head
Keywords plus
Language
english
Publication Year
2017
Prepublished in Year
2016
HGF-reported in Year
2016
ISSN (print) / ISBN
0008-5472
e-ISSN
1538-7445
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Volume: 77,
Issue: 3,
Pages: 623-631
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Publisher
American Association for Cancer Research (AACR)
Publishing Place
Philadelphia, Pa.
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0000-00-00
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0000-00-00
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0000-00-00
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Reviewing status
Peer reviewed
POF-Topic(s)
30205 - Bioengineering and Digital Health
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-505500-001
G-500390-001
Grants
Copyright
Erfassungsdatum
2016-11-25