Novel Water-Soluble TNT Metallofullerene Derivatives for Imaging Applications

This Small Business Technology Transfer (STTR) Phase I Project proposes to functionalize TNT-metallofullerenes with highly water-soluble, steric-stabilizing ligands and to evaluate these materials as general MRI(Magnetic Resonance Imaging) contrast agents. Classical endohedral metallofullerenes are produced in exceedingly low yields and are unstable in air. In contrast, the development of trimetallic-nitride-template (TNT) process by the investigators has allowed the production of a new class of extremely stable endohedral metallofullerenes in sufficient research quantities. Biomedical applications in diagnostic and therapeutic areas offer a near-term opportunity to utilize these materials because the quantities required for such applications are relatively small, and these nanomaterials offer unique advantages over current systems. The TNT process allows the encapsulation of 1-3 paramagnetic lanthanides, isolating the metals from the body. Preliminary data indicates that hydroxylated, gadolinium-containing TNT-metallofullerenes increase the proton relaxation rate of surrounding water molecules significantly over currently used gadolinium chelates. However, aggregation of typical hydroxylated fullerenes prevents their maximum efficiency and utility. Addition of large, highly soluble ligands is expected to promote enhanced water solubility, deter aggregation, and deliver an even larger enhancement over current gadolinium MRI contrast agents.