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Tumor-specific uptake of fluorescent bevacizumab-IRDye800CW microdosing in patients with primary breast cancer: a phase I feasibility study

Lamberts, L. E., Koch, M., de Jong, J. S., Adams, A., Glatz, J., Kranendonk, M. E. G., Terwisscha van Scheltinga, A. G. T., Jansen, L., de Vries, J., Lub-de Hooge, M. N., Schroder, C. P., Jorritsma-Smit, A., Linssen, M. D., Boer, de, E., van der Vegt, B., Nagengast, W. B., Elias, S. G., Oliveira, S., Witkamp, A., Mali, W. P. T. M., van der Wall, E., Van Diest, P. J., de Vries, E. G., Ntziachristos, V. & van Dam, G. M., 1-Jun-2017, In : Clinical Cancer Research. 23, 11, p. 2730-2741 12 p.

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  • Tumor specific uptake of fluorescent bevacizumab

    Final author's version, 12 MB, PDF document

  • Tumor-Specific Uptake of Fluorescent Bevacizumab–IRDye800CW Microdosing in Patients with Primary Breast Cancer A Phase I Feasibility Study

    Final publisher's version, 1 MB, PDF document

DOI

PURPOSE: to provide proof of principle of safety, breast tumor-specific uptake and positive tumor margin assessment of the systemically administered near-infrared fluorescent (NIRF) tracer bevacizumab-IRDye800CW targeting vascular endothelial growth factor (VEGF)-A in breast cancer patients.

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 co-registration of tumor tissue and healthy tissue.

RESULTS: None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared to 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 out 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 towards 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 tumor tissue.

Original languageEnglish
Pages (from-to)2730-2741
Number of pages12
JournalClinical Cancer Research
Volume23
Issue number11
Publication statusPublished - 1-Jun-2017

    Keywords

  • ENDOTHELIAL GROWTH-FACTOR, CONSERVING SURGERY, INDOCYANINE GREEN, OVARIAN-CANCER, SAFETY, IN-111-BEVACIZUMAB, ANGIOGENESIS, EXPRESSION, ANTIBODIES, MARGINS

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