There is a need for improved imaging techniques which specifically identify molecular features of glioma cells and which might be used to target antitumor therapies. Convection enhanced delivery is a powerful new technique for delivering targeted molecular therapeutics into the brain. However, this strategy is hindered by potential irregularity of distribution due to tumor cytoarchitecture and an inability to accurately monitor the distribution of the therapeutic agents during and after infusion. Water-soluble trigadolinium nitride endohedral metallofullerenes are an innovative nanotechnology with great potential due to their MRI T1 relaxivity characteristics, approximately two orders of magnitude greater than conventional contrast agents. The metallofullerenes can be affinity labeled for molecular targeting and can have lutetium (Lu) or terbium (Tb) substituted for Gd. Lutetium can be neutron-activated to form 177Lu, an isotope with excellent characteristics for delivering targeted interstitial radiotherapy, while Tb can be visualized due to its fluorescence. We propose a strategy for developing affinity-labeled metallofullerenes as a powerful and innovative nanotechnology platform for targeting glioma cells in vivo, with Gd for MR imaging, with Tb for fluorescence localization, and with Lu for interstitial molecular brachytherapy. The proposed work brings together a number of innovative strategies to develop a nanotechnology platform for planning """"""""real-time"""""""" optimal delivery of intra-tumoral therapy. Summary: This project will develop, modify, and characterize metallofullerenes (""""""""buckyballs"""""""") as a nanotechnology platform capable of greatly improving brain tumor imaging and of delivering fluorescent labeling and radiation therapy to the tumor cells at the molecular level. Improvements in the detection and treatment of this devastating disease are desperately needed. The ability to simultaneously detect and target therapies at the brain tumor cells holds great promise. Lead Investigators: PP FATOUROS, PhD, Principal Investigator, expert in experimental and clinical imaging, Chair Radiation Physics & Biology; HC DORN, PhD (Virginia Tech), organic chemist and co-inventor of metallofullerenes; WC BROADDUS, MD, PhD, neurosurgeon scientist and Director VCD Neurooncology; J.D. WILSON, PhD, radiobiologist and Director Animal Imaging, VCU Molecular Imaging Center; H. L. FILLMORE, PhD, molecular neurobiologist, expert in tumor targeting strategies.
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