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

基本信息

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
项目类别：
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

项目摘要

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，包括星形胶质细胞瘤、少突胶质细胞瘤或室管膜瘤，约占所有脑癌的 70%。最常见的形式是多形性胶质母细胞瘤，仍然是最致命的胶质瘤形式。图像引导干预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) 是一种对于这些病变的诊断、评估和治疗的所有阶段都至关重要的成像剂。然而，目前的显像剂由于几个问题其有效性受到限制。因此，需要新的“综合”药物，将改进的成像灵敏度与改善诊断和结果的干预策略结合起来。 Luna Nanoworks 开发了新型含钆 (Gd) C60 内嵌金属富勒烯 (Gd3N@C80)，可作为开发集成图像引导系统的平台。该提案的目标是开发一种图像引导系统，将特定的肿瘤靶向能力与改进的成像能力相结合。我们将使用 Luna Innovations 专有的 Gd3N@C80 分子作为平台，该分子与当前的显像剂相比显然更敏感，可以通过各种治疗剂和/或试剂进行衍生化和功能化，从而改善治疗。我们假设 Gd3N@C80 纳米颗粒可以足够数量生产，并用分子进行化学修饰，从而增加其溶解度、被神经胶质瘤细胞吸收并改善肿瘤可视化。为了检验这一假设，我们将首先合成并表征 Gd3N@C80- 衍生物，作为神经胶质瘤靶向内嵌体 (GTE)，其功能基团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结合将使我们能够建立一个基线，以使用胶质瘤靶向 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：脑部癌症（例如多形性胶质母细胞瘤）很难诊断和治疗。 Luna Nanoworks 开发的纳米材料与现有试剂相比具有卓越的诊断能力。我们将使用这些分子作为开发集成图像引导系统的平台，该系统将改善脑癌的诊断和治疗。