The object of the proposed research plan is to develop a widespread clinical agent with improved tracer kinetics. The requisite for an optimal myocardial extraction characteristics and improved tracer kinetics. The requisite for an optimal myocardial blood flow imaging agent is accumulation in myocardium in proportion to true blood flow with prolonged retention in the myocardium. Such an agent would provide improved detection of mild coronary artery stenoses compared with other commercially available myocardial perfusion tracers. Radiolabeled rotenone analogs have been shown to posses excellent myocardial extraction characteristics over a range of blood flow making them promising clinical myocardial perfusion tracers. In this proposal we plan to develop a series of Technetium-99, (Tc-99m) labeled rotenone analogs and evaluate their myocardial kinetics compared to other flow tracers. The proposed research will determine the optimal structure features of technetium-99m labeled rotenone for the development of a myocardial blood flow imaging agent for nuclear medicine. Four [Tc- 99m) rotenone compounds containing different Tc-99m-chelation moieties will be synthesized and their myocardium extraction and biodistribution studied in rats.
Identification of an agent that accurately delineates myocardial flow non- invasively, would be of considerable benefit in the diagnosis and treatment of heart disease. The current market for cardiac flow tracers is greater than $300 million dollars per year. An improved product means increased market growth and improved patient care. In turn, accurate diagnosis affords improved patient management, and ultimately results in lower healthcare costs.
