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Cancer Res. 2017 Feb 1;77(3):623-631. doi: 10.1158/0008-5472.CAN-16-1773. Epub 2016 Nov 22.

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

Author information

1
Chair for Biological Imaging, Technical University of Munich, München, Germany.
2
Institute for Biological and Medical Imaging, Helmholtz Zentrum München, München, Germany.
3
Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
4
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
5
Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands.
6
Hospital and Clinical Pharmacy, University of Groningen, University Medical Center Groningen, the Netherlands.
7
Research Unit Analytical Pathology, Helmholtz Zentrum München, München, Germany.
8
Department of Surgery, University of Groningen, University Medical Center Groningen, the Netherlands.
9
Department of Pathology, University of Groningen, University Medical Center Groningen, the Netherlands.
10
Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
11
Julius Center for Health Sciences and Primary Care, Cell Biology, University Medical Center Utrecht, Utrecht, the Netherlands.
12
Department of Biology, University Medical Center Utrecht, Utrecht, the Netherlands.
13
Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
14
Department of Medical Oncology, Utrecht University, University Medical Center Utrecht, Utrecht, the Netherlands.
15
Department of Nuclear Medicine and Molecular Imaging and Intensive Care, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
16
Chair for Biological Imaging, Technical University of Munich, München, Germany. v.ntziachristos@tum.de.

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.

PMID:
27879266
DOI:
10.1158/0008-5472.CAN-16-1773
[Indexed for MEDLINE]
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