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

Maximilian Koch, Johannes S. de Jong, Juergen Glatz, Panagiotis Symvoulidis, Laetitia E. Lamberts, Arthur L. L. Adams, Mariette E. G. Kranendonk, Anton 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 OliveiraArjen 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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)

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 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
Volume77
Issue number3
DOIs
Publication statusPublished - 1-Feb-2017

Keywords

  • INDOCYANINE GREEN
  • FOLATE
  • SURGERY
  • MARGINS
  • SAFETY
  • AGENT
  • HEAD

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