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.

长期目标是开发并将PE特异性放射成像探针99 mTcHYNIC-Duramycin应用于临床，该探针可检测细胞凋亡，用于高危动脉粥样硬化斑块的成像。具体目的包括1）检查螯合剂间隔臂对放射性示踪剂的影响，2）开发分离两种单缀合异构体以检查其结合亲和力的方法，3）比较TPPTS和EDDA作为共配体并使用甘露醇作为填充剂以优化用于示踪剂制备的冻干小瓶试剂盒，和4）使用优化的探针和最终的小瓶试剂盒制剂证明在兔模型中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，将为进一步的II期开发提供合格的分子成像探针。II期研究将包括在冠状动脉斑块的大型动物模型中评价成像探头和探头安全性表征，以支持IND提交。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（严重衰弱性冠状动脉事件的原因）提供急需的工具。评估动脉粥样硬化的程度和识别急性心血管事件的高风险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.