Development and Testing of New Tissue-Specific Radiopharmaceuticals
The development and testing of new tissue-specific radiopharmaceuticals for in vivo nuclear imaging and therapeutic applications are important research areas. A variety of agents are currently being developed for tumor therapy, which are being evaluated in animal models and have shown good therapeutic effectiveness (See following sections describing rhenium-188 and bismuth-213). A key example of a diagnostic agent is the research and clinical use for evaluation of myocardial viability of the methyl-branched BMIPP fatty acid analogue which was developed in the ORNL Nuclear Medicine Program. Iodine-125-labeled BMIPP is continuing clinical trials at several institutions in the United States and Europe and has been marketed in Japan by Nihon Medi-Physics, Inc., since 1993, as an approved radiopharmaceutical named "Cardiodine®" for evaluation of myocardial viability. This agent has been used in several hundred thousand patient studies. BMIPP is currently in Phase III clinical trials at Zemiva® in the U.S. More recently, BMIPP has seen a renaissance as an important agent in cardiology research for the evaluation of fatty acid metabolism and trafficking in conjunction with studies of the physiology of the CD36 transport protein and the involvement of lipoproteins and foam cells in the atherosclerotic process. Using db/db diabetic mice, we have used BMIPP at ORNL and demonstrated for the first time unexpected alterations in lipid metabolism resulting from the nuclear targeting of agonists for the nuclear peroxisomal proliferator activated receptor (PPARgamma) which control gene expression and are used for resensitization of cells to insulin in Type II diabetes.