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: 9753714
• 负责人: Tayyaba Hasan
• 金额: $ 13.03万
• 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 2020-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9753714
• 关键词: 3-Dimensional; 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 Delivery Systems; 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; 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; Systems Development; Techniques; Testing; Therapeutic Agents; Tracer; Treatment Efficacy; Tumor Oxygenation; Tumor Tissue; Tyrosine Kinase Inhibitor; 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; liposomal delivery; mortality; mouse model; multimodality; 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

项目成果

Combined Fluorescence and Optoacoustic Imaging for Monitoring Treatments against CT26 Tumors with Photoactivatable Liposomes.

• DOI: 10.3390/cancers14010197
• 发表时间: 2021-12-31
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Turchin I;Bano S;Kirillin M;Orlova A;Perekatova V;Plekhanov V;Sergeeva E;Kurakina D;Khilov A;Kurnikov A;Subochev P;Shirmanova M;Komarova A;Yuzhakova D;Gavrina A;Mallidi S;Hasan T
• 通讯作者: Hasan T