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、少突细胞瘤或室管膜瘤，约占所有脑癌的70%。最常见的形式，多形性胶质母细胞瘤，仍然是最致命的胶质瘤。图像引导干预将肿瘤成像与干预联系起来。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，目前的显像剂的有效性受到几个问题的限制。因此，需要新的“综合”药物，将改善的成像敏感性与改善诊断和预后的干预策略结合起来。Luna Nanoworks开发了一种新型含钆（Gd）的C60内源性金属富勒烯（Gd3N@C80），可以作为开发集成图像制导系统的平台。本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，与目前的显像剂相比，它明显更敏感，作为一个平台，可以衍生和功能化各种治疗和/或药物，以改善治疗。我们假设Gd3N@C80纳米颗粒可以生产足够数量的化学修饰分子，从而增加其溶解度，被胶质瘤细胞吸收，并改善肿瘤的可见性。为了验证这一假设，我们将首先合成并表征Gd3N@C80-衍生物为胶质瘤靶向内啡肽（GTE），其官能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。解剖学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：脑癌如多形性胶质母细胞瘤难以诊断和治疗。Luna Nanoworks开发的纳米材料与目前的试剂相比，具有优越的诊断能力。我们将利用这些分子作为开发综合图像引导系统的平台，以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.