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

Abstract

<b>Purpose:</b> 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.<b>Experimental Design:</b> 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 <i>ex vivo</i> in surgical specimens using an optical imaging system. <i>Ex vivo</i> multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and coregistration of tumor tissue and healthy tissue.<b>Results:</b> None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared with those in the tumor margin (<i>P</i> < 0.05) and healthy tissue (<i>P</i> < 0.0001). VEGF-A tumor levels also correlated with tracer levels (<i>r</i> = 0.63, <i>P</i> < 0.0002). All but one tumor showed specific tracer uptake. Two of 20 surgically excised lumps contained microscopic positive margins detected <i>ex vivo</i> by fluorescent macro- and microscopy and confirmed at the cellular level.<b>Conclusions:</b> 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 <i>in vivo</i> margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in the tumor tissue. <i>Clin Cancer Res; 23(11); 2730-41. ©2016 AACR</i>.