Tumor-specific uptake of fluorescent bevacizumab-IRDye800CW microdosing in patients with primary breast cancer: A phase I feasibility study
Lamberts LE, Koch M, De Jong JS, Adams ALL, Glatz J, Kranendonk MEG, Van Scheltinga AGTT, Jansen L, De Vries J, Hooge MNLD, Schroder CP, Jorritsma-Smit A, Linssen MD, De Boer E, Van Der Vegt B, Nagengast WB, Elias SG, Oliveira S, Witkamp AJ, Mali WPTM, Van Der Wall E, Van Diest PJ, De Vries EGE, Ntziachristos V, Van Dam GM (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 23
Pages Range: 2730-2741
Journal Issue: 11
DOI: 10.1158/1078-0432.CCR-16-0437
Abstract
Purpose: 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-IRDye800CWtargeting VEGF-A in patientswith breast cancer. Experimental Design: 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 ex vivo in surgical specimens using an optical imaging system. Ex vivo multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and coregistration of tumor tissue and healthy tissue. Results: None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared with those in the tumor margin (P < 0.05) and healthy tissue (P < 0.0001). VEGF-A tumor levels also correlated with tracer levels (r = 0.63, P < 0.0002). All but one tumor showed specific tracer uptake. Two of 20 surgically excised lumps contained microscopic positive margins detected ex vivo by fluorescent macro- and microscopy and confirmed at the cellular level. Conclusions: 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 in vivo margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in the tumor tissue.
Involved external institutions
University of Groningen / Rijksuniversiteit Groningen
Netherlands (NL)
Technische Universität München (TUM)
Germany (DE)
Universiteit Utrecht (UU) / Utrecht University
Netherlands (NL)
Netherlands (NL)
Technische Universität München (TUM)
Germany (DE)
Universiteit Utrecht (UU) / Utrecht University
Netherlands (NL)
How to cite
APA:
Lamberts, L.E., Koch, M., De Jong, J.S., Adams, A.L.L., Glatz, J., Kranendonk, M.E.G.,... Van Dam, G.M. (2017). Tumor-specific uptake of fluorescent bevacizumab-IRDye800CW microdosing in patients with primary breast cancer: A phase I feasibility study. Clinical Cancer Research, 23(11), 2730-2741. https://doi.org/10.1158/1078-0432.CCR-16-0437
MLA:
Lamberts, Laetitia E., et al. "Tumor-specific uptake of fluorescent bevacizumab-IRDye800CW microdosing in patients with primary breast cancer: A phase I feasibility study." Clinical Cancer Research 23.11 (2017): 2730-2741.
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