A New Class of Trimetasphere Based Radiopharmaceuticals

73097S03-I In nuclear medicine, commonly employed radiopharmaceuticals generally utilize chelated radioisotopes of metals for diagnostic and therapeutic applications. However, the in vivo kinetic stability of radiometal agents remains a major concern for any new radiopharmaceutical. Endohedral metallofullerenes would have an inherent advantage due to the high stability of the carbon cage and characteristic resistance to any metabolic cage-opening process. In this project, a lutetium member of a new class of highly stable endohedral metallofullerenes, lutetium trimetaspheres, will be functionalized and neutron activated. Yields, cross-sections, and decay products will be determined. The advantage of these new materials over existing radiopharmaceuticals is the ability to capture three active atoms within the carbon cage, where they are sequestered from the surrounding organic matrix. Phase I will synthesize and purify a quantity of lutetium trimetaspheres, functionalize them with appropriate ligands, and have them neutron activated at a national laboratory. This will allow verification of the activation cross sections and qualification of yields and decay products. Commercial Applications and Other Benefits as described by the awardee: Lutetium trimetasphere radiopharmaceuticals should be more potent and more targetable than other chelated lutetium agents due to their unique nanostructure. Such a product would represent a significant improvement in treatment, with a concomitant reduction of mortality.