Novel Tc-99m labeled rotenone complexes cardiac imaging

提出的研究计划的目的是开发一种具有改进示踪动力学的广泛应用的临床药物。需要一个最佳的心肌提取特性和改进的示踪动力学。最佳心肌血流显像剂的必要条件是在心肌中的积累与真血流量成比例，并在心肌中长时间滞留。与其他市售的心肌灌注示踪剂相比，这种药物可以更好地检测轻度冠状动脉狭窄。放射性标记鱼藤酮类似物已被证明具有出色的心肌提取特性，在一定范围内的血流使其成为有前途的临床心肌灌注示踪剂。在本提案中，我们计划开发一系列锝-99 （Tc-99m）标记的鱼tenone类似物，并与其他血流示踪剂相比评估其心肌动力学。本研究将确定锝-99m标记鱼藤酮的最佳结构特征，用于核医学心肌血流显像剂的开发。本文将合成四种含有不同Tc-99m螯合基团的[Tc- 99m]鱼藤酮化合物，并研究其在大鼠心肌中的提取和生物分布。建议的商业应用：鉴定一种能无创准确描绘心肌血流的药物，将在心脏病的诊断和治疗中有相当大的好处。目前，心脏血流追踪器的市场规模每年超过3亿美元。改进的产品意味着增加市场增长和改善患者护理。反过来，准确的诊断可以改善患者管理，并最终降低医疗保健成本。

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. PROPOSED COMMERCIAL APPLICATIONS: 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.