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.
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. ? ? ?
| MacFarland, Darren K; Walker, Kenneth L; Lenk, Robert P et al. (2008) Hydrochalarones: a novel endohedral metallofullerene platform for enhancing magnetic resonance imaging contrast. J Med Chem 51:3681-3 |
