Development of Glioblastoma-Targeting Endofullerenes for Imaging Brain Tumors

开发用于脑肿瘤成像的胶质母细胞瘤靶向内富勒烯

• 批准号: 7537825
• 负责人: Chris L KEPLEY
• 金额: $ 15.02万
• 依托单位: LUNA INNOVATIONS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-22 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7537825
• 关键词: Accounting; Amines; Benign; Binding; Blood - brain barrier anatomy; Brain; Brain Neoplasms; Brain imaging; Cell Line; Cells; Characteristics; Chemicals; Contrast Media; Cytoplasm; Data; Detection; Development; Diagnosis; Diagnostic; Dose; Effectiveness; Encapsulated; Endocytosis; Excision; Fluorescence; Folate; Fullerenes; Gadolinium; Gadopentetate Dimeglumine; Glioblastoma; Glioma; Goals; Image; Imagery; Imaging Techniques; Intervention; Lesion; Link; Liposomes; Magnetic Resonance Imaging; Malignant Glioma; Malignant Neoplasms; Malignant neoplasm of brain; Mitochondria; Molecular; Monitor; Necrosis; Normal tissue morphology; Operative Surgical Procedures; Outcome; Phase; Physicians; Public Health; Radiation; Research; Risk; Solubility; Surface; Survival Rate; System; Techniques; Testing; Therapeutic; Therapeutic Agents; Water; base; cancer diagnosis; cancer imaging; cancer therapy; carboxyl group; cell type; diagnosis evaluation; functional group; image guided intervention; improved; in vivo; innovation; metal poisoning; nanomaterials; nanoparticle; neoplastic cell; novel; receptor; tumor; uptake; water solubility

DESCRIPTION (provided by applicant): Malignant gliomas, including astrocytic, oligodendrological, or ependymal, account for approximately 70% all brain cancers. The most common form, glioblastoma multiform, remains the deadliest form of glioma. Image-guided interventions link imaging of tumors to interventions. Magnetic Resonance Imaging (MRI) using contrast agents is one type of imaging agent critical for all phases in the diagnosis, evaluation and treatment of these lesions. However, current imaging agents are limited in their effectiveness based on several problems. Therefore, new "integrated" agents are needed that combine improved imaging sensitivities with intervention strategies that improve diagnoses and outcomes. Luna Nanoworks has developed novel gadolinium (Gd)-containing C60 endohedral metallofullerenes (Gd3N@C80) that can serve as a platform for developing integrated, image-guidance systems. The goal of this proposal is to develop an image-guided system that would allow for specific tumor targeting capabilities integrated with improved imaging capabilities. We will use Luna Innovations proprietary Gd3N@C80 molecules, which are demonstrably more sensitive compared to current imaging agents, as a platform which can be derivatized and functionalized with various therapeutics and/or agents that improve treatments. We hypothesize that the Gd3N@C80 nanoparticles can be produced in sufficient enough quantities to be chemically modified with molecules that will increase their solubility, uptake into glioma tumor cells, and improve tumor visualization. To test this hypothesis we will first synthesize and characterize the Gd3N@C80- derivatives as glioma-targeting endohedrals (GTE) with functional groups that will enhance tumor targeting and visualization. Next we will examine the cellular uptake of GTE using glioblastoma cell lines. The combination of anatomical imaging and dynamic contrast data will allow us to establish a baseline to use the glioma-targeting Gd3N@C80 for the development and optimization of fully integrated cancer imaging, monitoring, and therapy systems. PUBLIC HEALTH RELEVANCE: Cancers of the brain such as glioblastoma multiform are difficult to diagnose and treat. Luna Nanoworks has developed nanomaterials that have superior diagnostic capabilities compared to current agents. We will use these molecules as a platform for developing integrated, image-guidance systems that will improve in the diagnosis and treatment of cancers of the brain.

描述（由申请人提供）：恶性神经胶质瘤，包括星形胶质细胞，寡构或室心膜，约占所有脑癌的70％。最常见的形式是多形的胶质母细胞瘤，仍然是神经胶质瘤的最致命形式。图像引导的干预措施将肿瘤成像与干预措施联系起来。使用造影剂的磁共振成像（MRI）是对这些病变的诊断，评估和治疗中所有阶段至关重要的一种成像剂。但是，基于几个问题，当前的成像剂的有效性受到限制。因此，需要新的“综合”代理，将改进的成像敏感性与改善诊断和结果的干预策略相结合。 Luna Nanoworks开发了新型Gadolinium（GD） - 含有C60的C60内膜金属氟烯烯（GD3N@C80），可以用作开发集成的图像引物系统的平台。该建议的目的是开发图像引导的系统，该系统将允许与改进的成像功能集成的特定肿瘤靶向能力。我们将使用Luna创新专有的GD3N@C80分子，与当前的成像剂相比，它们显着敏感，作为一个平台，可以通过各种治疗剂和/或改善处理方法进行衍生化和功能化。我们假设可以用足够量的分子对GD3N@C80纳米颗粒进行化学修饰，从而增加其溶解度，摄取对神经胶质瘤肿瘤细胞的摄取并改善肿瘤可视化。为了检验这一假设，我们将首先合成并表征GD3N@C80-衍生物是伴有胶质瘤靶向的内联体（GTE），其功能组将增强肿瘤靶向和可视化。接下来，我们将使用胶质母细胞瘤细胞系检查GTE的细胞摄取。解剖成像和动态对比数据的组合将使我们能够建立一个基线，以使用靶向神经胶质瘤的GD3N@C80来开发和优化完全集成的癌症成像，监测和治疗系统。公共卫生相关性：诸如胶质母细胞瘤多形的大脑癌很难诊断和治疗。 Luna Nanoworks开发了与当前药物相比，具有较高诊断能力的纳米材料。我们将使用这些分子作为开发综合图像指导系统的平台，这些平台将改善大脑癌症的诊断和治疗。