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Supplemental Materials and Methods and Supplementary Figures 1 and 2 from Threshold Analysis and Biodistribution of Fluorescently Labeled Bevacizumab in Human Breast Cancer

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posted on 2023-03-31, 00:48 authored by Maximilian Koch, Johannes S. de Jong, Jürgen Glatz, Panagiotis Symvoulidis, Laetitia E. Lamberts, Arthur L.L. Adams, Mariëtte E.G. Kranendonk, Anton G.T. Terwisscha van Scheltinga, Michaela Aichler, Liesbeth Jansen, Jakob de Vries, Marjolijn N. Lub-de Hooge, Carolien P. Schröder, Annelies Jorritsma-Smit, Matthijs D. Linssen, Esther de Boer, Bert van der Vegt, Wouter B. Nagengast, Sjoerd G. Elias, Sabrina Oliveira, Arjen J. Witkamp, Willem P.T.M. Mali, Elsken Van der Wall, P. Beatriz Garcia-Allende, Paul J. van Diest, Elisabeth G.E. de Vries, Axel Walch, Gooitzen M. van Dam, Vasilis Ntziachristos

Supplemental Materials and Methods; Suppl. Fig. 1. Comparison of tumor vs. skin fluorescence obtained from human breast tissue specimen; Suppl. Fig 2: Magnified comparison between fluorescence images obtained from 3mm thick paraffin slices and 4microm paraffin slices.

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Leibniz Prize

Center for Translational Molecular Medicine

ERC

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ARTICLE 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. Cancer Res; 77(3); 623–31. ©2016 AACR.

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    Cancer Research

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    Breast CancerClinical ImagingClinical Trial ResultsSurgical Oncology

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