Optical imaging guided resection and photodynamic therapy of glioma with targeted photoactivable agents

项目描述 胶质母细胞瘤（GBM）是一种毁灭性的疾病，其生存率统计数据令人沮丧（总体为2-5%）。复发性 造成大多数死亡的疾病是局部的（95%），距离切除床只有几毫米。完全手术 切除术很少可行，因为GBM细胞侵入性生长到周围的正常脑组织中， 大块肿瘤此外，这些浸润细胞是高度迁移的，并表现出生化改变， 增加治疗阻力。利用荧光法显著延长生存时间（约28%） 引导切除术（FGR），然后进行光动力疗法（PDT，一种基于光化学的疗法），我们 其他人则致力于机械设计的PDT联合疗法，以治疗耐药癌症 细胞，我们建议在浸润性GBM细胞中特异性靶向表皮生长因子受体（EGFR 我们称之为靶向光活化多药疗法， 脂质体（TPMALs）与图像引导剂量测定。TPMAIL将整合FDA批准的PDT药物 （苯并卟啉衍生物，BPD）、成像造影剂（IRDye 800）和多RTK抑制剂。EGFR是 70%的浸润性耐药GBM表达。BPD和近红外示踪剂IRDye® 800 CW 结合到TPMAL膜中能够实现多波长荧光和光声成像， 用于PDT光剂量测定设计的TPMAL递送至残留的、不可切除的疾病的在线报告者， 治疗反应监测。拟议的研究提供了一个令人信服的机会， Hasan博士在美国的实验室（PDT和纳米药物输送系统）和Turchin博士的实验室的专业知识 （生物光子学和多模态荧光和光声成像系统），以解决 通过利用纳米技术和光学成像的进步， 组生物学（体外和体内）和纳米表征实验将在Hasan进行 实验室和技术方面（成像系统开发、模拟和数据/图像处理） 在Turchin实验室进行。哈桑博士高度互补的研究实验室之间的合作 Turchin将建立一个基于纳米技术的图像引导定制治疗平台， 快速评估联合治疗的疗效，并具有很高的潜力，临床翻译的成功， PDT和图像引导切除术治疗GBM。两个团队都期待着在项目之外继续努力， 从科学上讲，这里开发的技术具有透明地适应其他技术的巨大潜力 癌症类型。

Project Description Glioblastoma (GBM) is a devastating disease with dismal statistics for survival (2–5% overall). Recurrent disease responsible for most mortality is local (95%) few mm from the resection bed. Complete surgical resection is rarely feasible due to the invasive growth of GBM cells into normal brain tissue surrounding the bulk tumor. Moreover, these infiltrative cells are highly migratory and exhibit biochemical alterations that give rise to treatment resistance. Leveraging the significant increase (~28%) in survival time using fluorescence guided resection (FGR) followed by photodynamic therapy (PDT, a photochemistry based therapy) and our and others works on mechanistically designed PDT-based combination therapies to treat drug-resistant cancer cells, we propose to specifically target the epidermal growth factor receptor (EGFR) in infiltrative GBM cells beyond the margins of surgical resection in an approach we term as Targeted Photoactivatable Multi-Agent Liposomes (TPMALs) with image-guided dosimetry. The TPMAILs will integrate an FDA-approved PDT agent (benzoporphyrin derivative, BPD), an imaging contrast agent (IRDye800) and a multi-RTK inhibitor. EGFR is expressed in 70% of infiltrative drug resistant GBMs. BPD and a near-infrared tracer IRDye®800CW incorporated into the TPMAL membrane enable multi-wavelength fluorescence and photoacoustic imaging as online reporters of TPMAL delivery to residual, unresectable disease for PDT light dosimetry design and treatment response monitoring. The proposed study provides a compelling opportunity to bring together expertise of Dr. Hasan's lab (PDT and nano-drug delivery systems for cancer) in USA and Dr. Turchin's lab (Biophotonics and multi-modality fluorescence and photoacoustic imaging systems) in Russia to address the challenges mentioned above by leveraging advances in nanotechnology and optical imaging from both the groups. The biological (in vitro and in vivo) and nano-characterization experiments will be performed at Hasan lab and the technical aspects (imaging system development, simulations and the data/image processing) performed at Turchin lab. The collaboration between the highly complementary research labs of Drs. Hasan and Turchin will establish a nanotechnology based image-guided customized treatment platform capable of rapidly evaluating combination therapy efficacy and has high potential for clinical translation given the success of PDT and image-guided resection in GBM. Both teams look forward to continue efforts beyond the project as scientifically the techniques developed here have tremendous potential for transparent adaption to other cancer types.