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

光学成像引导的神经胶质瘤切除和光动力治疗与靶向光活化剂

• 批准号: 9381959
• 负责人: Tayyaba Hasan
• 金额: $ 13.11万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9381959
• 关键词: Address; Animal Experiments; Antibodies; BAY 54-9085; Beds; Biochemical; Biological; Biological Assay; Biophotonics; Blood; Brain; Cells; Clinical Trials; Collaborations; Combined Modality Therapy; Contrast Media; Custom; Data; Diagnostic; Disease; Dose; Drug Combinations; Drug Kinetics; Drug resistance; Encapsulated; Epidermal Growth Factor Receptor; Excision; Exhibits; FDA approved; Failure; Fluorescence; Glioblastoma; Glioma; Goals; Growth; Hydrophobicity; Image; Imaging Techniques; In Vitro; Infiltration; KDR gene; Light; Liposomes; Malignant Neoplasms; Malignant neoplasm of pancreas; Mediating; Membrane; Methods; Modality; Modeling; Monitor; Monoclonal Antibody C225; Multimodal Imaging; Nanotechnology; Nature; Neoplasm Metastasis; Nervous System Physiology; Noise; Operative Surgical Procedures; Outcome; PUVA Photochemotherapy; Pathway interactions; Patients; Penetration; Performance; Photobleaching; Photochemistry; Photosensitization; Phototherapy; Pilot Projects; Polymers; Positioning Attribute; Postdoctoral Fellow; Radio; Receptor Protein-Tyrosine Kinases; Recurrence; Recurrent disease; Reporter; Research; Resected; Residual Tumors; Residual state; Resolution; Russia; Sampling; Signal Transduction; Specificity; Surface; Surgical margins; Survival Rate; System; Systems Development; Techniques; Testing; Therapeutic Agents; Tracer; Treatment Efficacy; Tumor Oxygenation; Tumor Tissue; Unresectable; Work; angiogenesis; aqueous; base; brain tissue; cancer cell; cancer imaging; cancer type; chromophore; clinical translation; contrast imaging; conventional therapy; cytotoxic; density; design; dosimetry; experimental study; fluorescence imaging; image guided; image processing; imaging system; in vivo; individualized medicine; kinase inhibitor; liposomal delivery; mortality; mouse model; nano; nanodrug; nanoparticle; optical imaging; outcome forecast; photoacoustic imaging; quantitative imaging; receptor expression; response; simulation; statistics; success; therapy resistant; time use; treatment planning; treatment response; tumor; tumor growth

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.

项目描述 胶质母细胞瘤（GBM）是一种毁灭性疾病，生存期的统计数字很差（总体上为2-5％）。经常性 造成大多数死亡率的疾病是局部（95％）的切除床几毫米。完整的手术 由于GBM细胞在周围的正常脑组织中的侵入性生长，切除很少可行 散装肿瘤。此外，这些浸润细胞是高度迁移和暴露的生化改变 提高耐药性。利用荧光利用生存时间的显着增加（约28％） 指导切除（FGR），然后进行光动力疗法（PDT，基于光化学的治疗）和我们的 其他人则从事机械设计的基于PDT的组合疗法来治疗耐药性癌症 细胞，我们建议在浸润GBM细胞中特异性靶向表皮生长因子受体（EGFR） 除了手术切除的边缘以外，我们以一种靶向光活化的多代理而被称为 脂质体（TPMails）带有图像引导的剂量测定法。 TPMails将集成由FDA批准的PDT代理 （苯二甲培来衍生物，BPD），成像对比剂（IRDYE800）和多RTK抑制剂。 EGFR是 在70％的浸润药物GBM中表达。 BPD和近红外示踪剂IRDYE®800CW 掺入TPMAL膜中，使多波长的荧光和光声成像作为 TPMAL将在线交付到残留的，不可切除的疾病的在线记者，用于PDT轻剂量测定设计和 治疗反应监测。拟议的研究提供了一个令人信服的机会来汇集 Hasan博士实验室（PDT和纳米药物癌症的癌症）和Turchin博士实验室的专业知识 （俄罗斯的生物光谱和多模式荧光和光声成像系统） 在利用两者的纳米技术和光学成像的进步提出的挑战 组。将在Hasan进行生物学（体外和体内）和纳米特征实验 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 Lab进行。 DRS高度互补的研究实验室之间的合作。哈桑 Turchin将建立一个基于纳米技术的基于图像指导的定制治疗平台 快速评估组合疗法效率，并具有很高的临床翻译潜力 GBM中的PDT和图像引导切除术。两支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巨大的对其他适应的潜力 癌症类型。