New MR Angiography Agents Using Gd@C60 Nanotechnology

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DESCRIPTION (provided by applicant): This project will create a new class of MRI contrast agents for angiography based on Gd-C60 nanotechnology. Gd-containing endohedral metallofullerenes, having a total lack of free Gd3+ dissociation, will be safer than conventional linear and macrocyclic Gd3+ chelates; this is especially important for contrast agents with the prolonged half-lives needed for angiography. The endohedral metallofullerene Gd-C60 has shown considerable promise as a new platform for a unique class of safe and effective paramagnetic blood-pool contrast agents. Preliminary results obtained with the compound Gd-C60(C(COOH)2)10 revealed it to be an efficient MRI contrast agent (rl = 4.7 mM-lsec-1 at 40 deg C and 0.47 T). In addition, it is the first water soluble endohedral metallofullerene compound with a favorable biodistribution. New Gd-C60 derivatives synthesized in this project will be based on this compound, but will bear a mixture of neutral and anionic charged hydrophilic groups as well as other hydrophobic groups. These new compounds will feature lowered osmolality while having high affinities for the serum protein albumin. These features will increase both blood-pool residence times and relaxivity values. Physical and relaxometric studies will characterize the efficacy of this new class of blood-pool MRI contrast enhancing agents. The new Gd-C60 compounds created in this study will fill a unique niche in angiographic MR imaging applications, for example the non-invasive detection of vascular abnormalities, while exceeding the safety levels of current Gd chelates.