Optical Imaging to Improve Surgery & Targeted Therapy in Brain Tumors

项目摘要 脑瘤患者的总体存活率和预后仍然令人沮丧；大多数患者死于 他们的病。这些患者的希望取决于进行更准确的手术切除并增加 治疗药物对血脑屏障的渗透。我们建议使用基于抗体的成像 提高肿瘤切除范围和发展量化和提高效率的新方法的战略 在这种毁灭性疾病中的抗体传递。 我们建议使用针对标记的表皮生长因子受体(EGFR)的抗体(Panitumumab) 使用近红外荧光团(IRDye800)在计划在脑肿瘤患者中进行首次人体试验 接受手术切除。对于我们的临床研究，我们将首先评估其敏感性和特异性。 Panitumumab-IRDye800用于检测不同剂量研究药物的脑瘤并评估其安全性。然后 我们建议对肿瘤和瘤周组织中的抗体传递进行定量，并与术前相关。 用于预测抗体递送增加的成像。此外，我们将确定对血脑的操纵是否 屏障可以改善抗体进入肿瘤的传递，利用荧光标记抗体的使用来 追踪抗体进入肿瘤的情况。通过这一应用，我们希望提高肿瘤的可视化在 外科手术和开发技术来预测抗体输送到脑瘤。这将是第一次 荧光标记的抗体用于术中抗体的实时成像和定量 投递到人脑肿瘤。

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.