The artificial element technetium, in the form of its short-lived gamma ray emitting radionuclide 99mTc, plays a very important role in routine nuclear medicine imaging. More than 85% of all procedures in the USA involve the administration of a 99mTc-labeled radiopharmaceutical. This renewal application describes a continuing program of research that combined basic chemical studies of the element together with applications of that chemistry towards the design of new imaging agents. In addition a parallel program will explore the chemistry of the closely related metallic element rhenium and its applications in radiotherapy. The basic studies of technetium will include the use of new synthetic intermediates discovered in the current cycle to explore the rapidly developing low-oxidation-state chemistry, the use of nitrogen donor ligands to form new complexes in low and high oxidation states, and an investigation of its organometallic chemistry. New strategies will be investigated for conjugation of technetium to biologically active molecules using several different classes of complexes that leave free coordinating sites for the attachment of biological ligands. The first application of the chemistry will involve an investigation of a variety of cationic technetium complexes as myocardial imaging agents that are sensitive to the metabolic state of the tissue. Such agents would be important in the evaluation of salvageable tissue following an ischemic event. The second area will explore several avenues towards tumor detection, including relatively simple cationic complexes and 99mTc-labeled natural killer (NK) cells. In the applications of rhenium chemistry, reliable methods for synthesizing required compounds at tracer concentrations will be devised. This will essentially parallel earlier developments in technetium chemistry. This chemistry will then be applied to a search for soluble agents suitable for radiation synovectomy, particularly for treatment of rheumatoid arthritis and pigmented villonodular synovitis. The use of soluble agents may allow a wider use of this therapy in joints smaller than the knee and ankle.
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