IGF::OT::IGF SBIR TOPIC 85 TO SUPPORT THE DEVELOPMENT OF TARGET SPECIFIC MOLECULAR IMAGING AGENTS IN COMBINATION WITH EXISTING IMAGING MODALITIES TO DETECT HIGH RISK ATHEROSCLEROTIC PLAQUE.

长期目标是开发一种PE特异性放射成像探针99mTcHYNIC-杜拉霉素，并将其转化到临床，以检测细胞凋亡，用于高危动脉粥样硬化斑块的成像。具体目的包括1)检测螯合剂间隔臂对放射性示踪剂的影响，2)建立一种分离两种单共轭异构体的方法以检测它们的结合亲和力，3)比较TPPTS和EDDA作为共配体，并使用甘露醇作为填充剂来优化用于示踪剂制备的冻干试剂盒，以及4)使用优化的探针和最终试剂盒配方在兔模型上演示主动脉斑块成像的可行性。在兔主动脉斑块模型中对探针进行系统优化和概念验证后，将为进一步的II期开发提供合格的分子成像探针。第二阶段研究将包括在冠状动脉斑块的大型动物模型中评估成像探针，以及支持IND提交的探针的安全性特征。这种动脉粥样硬化斑块放射成像探头的成功开发将为临床识别高危冠状动脉斑块提供迫切需要的工具，高危斑块是严重削弱冠状动脉事件的原因。评估动脉粥样硬化的程度和确定急性心血管事件的高危患者具有重要的临床意义。

The long-term objective is to develop and translate to the clinic a PE-specific radioimaging probe, 99mTcHYNIC-Duramycin, shown to detect cellular apoptosis for the imaging of high-risk atherosclerotic plaque. The specific aims include 1) examining the affect of chelator spacer arms on the radiotracer, 2) developing a process to separate the two mono-conjugated isomers to examine their binding affinity, 3) comparing TPPTS and EDDA as co-ligands and use of mannitol as bulking agent to optimize the lyophilized vial kit for tracer preparation, and 4) demonstrating the aortic plaque imaging feasibility in a rabbit model using the optimized probe and final vial kit formulation. The systematic optimization of the probe followed by proof-of-concept in a rabbit aortic plaque model will provide a qualified molecular imaging probe for further phase II development. Phase II studies will include evaluation of the imaging probe in large animal models of coronary plaque and probe safety characterization to support an IND submission. The successful development of this atherosclerotic plaque radioimaging probe will provide an urgently needed tool for the clinical identification of high-risk coronary plaque, the cause of severe debilitating coronary events. Assessing the extent of atherosclerosis and identifying patients at high risk for an acute cardiovascular event is of significant clinical importance.