PROJECT ABSTRACT The overall survival and prognosis of patients suffering from brain tumors remain dismal; most patients die from their disease. Hope for these patients depends on performing more accurate surgical resections and increasing penetration of therapeutic drugs into the blood-brain barrier. We propose to use an antibody-based imaging strategy to improve extent of tumor resection and to develop new methods to quantify and increase the efficiency of antibody delivery in this devastating disease. We propose to use an antibody (panitumumab) targeting the epidermal growth factor receptor (EGFR) labeled with a near-infrared fluorophore (IRDye800) to conduct a first-in-human trial in brain tumor patients scheduled to undergo surgical resection. For our clinical study, we will first evaluate the sensitivity and specificity of panitumumab-IRDye800 to detect brain tumors at different doses of the study drug and assess its safety. Then we propose to quantitate antibody delivery into tumor and peritumoral tissue and correlate with pre-surgical imaging to predict increased antibody delivery. Furthermore, we will determine if manipulation of the blood-brain barrier can improve delivery of antibody into the tumor, leveraging the use of fluorescently labeled antibodies to track antibody delivery into the tumor. Through this application, we hope to improve tumor visualization during surgery and to develop techniques to predict antibody delivery to brain tumors. This would be the first time that a fluorescently-labeled antibody is used for real-time intraoperative imaging and quantification of antibody delivery to human brain tumors.

PROJECT NARRATIVE The overall survival and prognosis of patients depends on performing more accurate surgical resections and increasing penetration of therapeutic drugs into the blood-brain barrier. We propose to use an antibody-based imaging strategy to improve extent of tumor resection in a first in human clinical trial using fluorescently labeled antibodies. Furthermore, we propose to qualitatively and quantitatively measure antibody delivery into brain tumors in order to develop predictive markers for associated with increased the efficiency of antibody delivery in this devastating disease.