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Document type:
journal article 
Author(s):
Lamberts, Laetitia E; Koch, Maximillian; de Jong, Johannes S; Adams, Arthur L L; Glatz, Jürgen; Kranendonk, Mariëtte E G; Terwisscha van Scheltinga, Anton G T; Jansen, Liesbeth; de Vries, Jakob; Lub-de Hooge, Marjolijn N; Schröder, Carolien P; Jorritsma-Smit, Annelies; Linssen, Matthijs D; de Boer, Esther; van der Vegt, Bert; Nagengast, Wouter B; Elias, Sjoerd G; Oliveira, Sabrina; Witkamp, Arjen J; Mali, Willem P Th M; Van der Wall, Elsken; van Diest, Paul J; de Vries, Elisabeth G E; Ntziachris...    »
 
Title:
Tumor-Specific Uptake of Fluorescent Bevacizumab-IRDye800CW Microdosing in Patients with Primary Breast Cancer: A Phase I Feasibility Study. 
Abstract:
To provide proof of principle of safety, breast tumor-specific uptake, and positive tumor margin assessment of the systemically administered near-infrared fluorescent tracer bevacizumab-IRDye800CW targeting VEGF-A in patients with breast cancer. Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab-IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and in surgical specimens using an optical imaging system. multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and coregistration of tumor tissue and healthy tissue. None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared with those in the tumor margin (< 0.05) and healthy tissue (< 0.0001). VEGF-A tumor levels also correlated with tracer levels ( = 0.63,< 0.0002). All but one tumor showed specific tracer uptake. Two of 20 surgically excised lumps contained microscopic positive margins detected by fluorescent macro- and microscopy and confirmed at the cellular level. Our study shows that systemic administration of the bevacizumab-IRDye800CW tracer is safe for breast cancer guidance and confirms tumor and tumor margin uptake as evaluated by a systematic validation methodology. The findings are a step toward a phase II dose-finding study aimed at margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in the tumor tissue. . 
Journal title abbreviation:
Clin Cancer Res 
Year:
2017 
Journal volume:
23 
Journal issue:
11 
Pages contribution:
2730-2741 
Language:
eng 
Print-ISSN:
1078-0432 
TUM Institution:
Lehrstuhl für Biologische Bildgebung (Prof. Ntziachristos)