Threshold Analysis and Biodistribution of Fluorescently Labeled Bevacizumab in Human Breast Cancer

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., Aichler, M., Jansen, L., de Vries, J., Lub-de Hooge, M. N., Schroder, C. P., Jorritsma-Smit, A., Linssen, M. D., de Boer, E., van der Vegt, B., Nagengast, W. B., Elias, S. G., Oliveira, S., Witkamp, A. J., Mali, W. P. T. M., Van der Wall, E., Garcia-Allende, P. B., van Diest, P. J., de Vries, E. G. E., Walch, A., van Dam, G. M. & Ntziachristos, V., 1-Feb-2017, In : Cancer Research. 77, 3, p. 623-631 9 p.

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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 andnonmalignant 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 hybridmultiscale 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 thresh-old 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 tumormass. Overall, our results illustrate a quantitative approach to relate fluorescence signals to malignant tissues and improve the theranostic application of fluorescence molecular imaging. (C) 2016 AACR.

Original languageEnglish
Pages (from-to)623-631
Number of pages9
JournalCancer Research
Issue number3
Publication statusPublished - 1-Feb-2017



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