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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

基本信息

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
项目类别：
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

项目摘要

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