Optical Imaging to Improve Surgery & Targeted Therapy in Brain Tumors

项目摘要 患有脑肿瘤的患者的总体存活率和预后仍然令人沮丧;大多数患者死于 他们的疾病。这些患者的希望取决于进行更准确的手术切除， 治疗药物穿透血脑屏障。我们建议使用抗体成像 改善肿瘤切除范围的策略，并开发新的方法来量化和提高效率 在这种毁灭性疾病中的抗体传递。 我们建议使用靶向表皮生长因子受体（EGFR）标记的抗体（帕尼单抗）， 用近红外荧光团（IRDye 800）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 Panitumumumab-IRDye 800检测研究药物不同剂量下的脑肿瘤并评估其安全性。然后 我们建议定量抗体递送到肿瘤和瘤周组织中，并与术前 成像以预测增加的抗体递送。此外，我们将确定是否操纵血脑 屏障可以改善抗体向肿瘤中的递送，利用荧光标记抗体的使用， 追踪抗体进入肿瘤的过程通过这个应用程序，我们希望在手术过程中提高肿瘤的可视化。 并开发预测抗体向脑肿瘤递送的技术。这将是第一次 荧光标记抗体用于实时术中成像和抗体定量 输送到人类脑肿瘤中。

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.