Development of Glioblastoma-Targeting Endofullerenes for Imaging Brain Tumors

描述（由申请人提供）：恶性胶质瘤，包括星形细胞瘤、少突胶质瘤或室管膜瘤，约占所有脑癌的70%。最常见的形式，多形性胶质母细胞瘤，仍然是最致命的形式的神经胶质瘤。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）是一种对这些病变的诊断、评价和治疗的所有阶段都至关重要的成像剂。然而，基于若干问题，目前的成像剂在其有效性方面受到限制。因此，需要新的“综合”药剂，其将改善的成像灵敏度与改善诊断和结果的干预策略结合联合收割机。Luna Nanoworks开发了新型含钆（Gd）的C60内嵌金属富勒烯（Gd3N@C80），可以作为开发集成图像导航系统的平台。该提案的目标是开发一种图像引导系统，该系统将允许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，与当前的成像剂相比，该分子被证明更敏感，作为一个平台，可以用各种治疗剂和/或改善治疗的试剂衍生和功能化。我们假设Gd3N@C80纳米颗粒可以以足够的量产生，以用分子进行化学修饰，这将增加它们的溶解度，被神经胶质瘤肿瘤细胞摄取，并改善肿瘤可视化。为了验证这一假设，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角体（GTE），其具有增强肿瘤靶向和可视化的官能团。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，以使用神经胶质瘤靶向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：大脑的癌症，如胶质母细胞瘤是很难诊断和治疗的。Luna Nanoworks已经开发出纳米材料，与目前的药物相比，具有上级诊断能力。我们将使用这些分子作为开发集成的图像引导系统的平台，这些系统将改善脑癌的诊断和治疗。

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.