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的示踪剂动力学的广泛的临床药剂。最佳心肌提取特性和改进示踪剂动力学的必要条件。最佳心肌血流显像剂的必要条件是在心肌中与真实血流成比例地蓄积并在心肌中延长保留。与其他市售的心肌灌注示踪剂相比，这种试剂将提供对轻度冠状动脉狭窄的改进的检测。放射性标记的鱼藤酮类似物已被证明在血流范围内具有优异的心肌提取特性，使其成为有前途的临床心肌灌注示踪剂。在这个建议中，我们计划开发一系列的锝-99，（Tc-99 m）标记的鱼藤酮类似物，并评估其心肌动力学相比，其他流量示踪剂。本研究将探讨锝标记鱼藤酮的最佳结构特征，以开发心肌血流显像剂应用于核医学。本文合成了四种含不同Tc-99 m-螯合基团的[Tc-99 m]鱼藤酮化合物，并研究了它们的心肌提取和大鼠体内生物分布。拟议的商业应用：鉴定一种能准确无创描绘心肌血流的试剂，将对心脏病的诊断和治疗有相当大的益处。目前心脏血流示踪剂的市场每年超过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.