动脉易损斑块多成因靶标表达及时量变化规律的分子显像研究

Acute cardiac events are closely related with development of vulnerable artery plaque (VAP), but the further research on the mechanism of VAP is difficult for the reason that can not perform visual dynamic detection of VAP key targets and display their interaction in-vivo. Based on our preliminary research work, this study focus on three key tagets on VAP by molecular imaging using three new molecular probes (18F-FEDAA1106, 99mTc-Duramycin and 99mTc-RGD) that specially binds to respectively infiltrating macrophages, apoptotic cells and neovascularization in VAP. The purpose of our study is to detect abnormal molecular expression of the key targets in different arteriovascular VAP，reveal the relationship between their expression and the stability of the plaques, monitor dynamic changes of each key target expression on VAP progression and research the interaction of three targets in VAP dynamic evolution by in-vivo molecular imaging. Our study will be significantly helpful for providing more experimental evidences about molecular expessions in VAP evolution, and establish more effective moleculor imaging methods for visually monitoring VAP in-vivo.

急性心脏事件与动脉易损斑块（VAP）有关，目前研究观点认为侵润巨噬细胞、凋亡细胞和新生微血管与VAP形成密切相关，但三者之间的相互关系和动态演进变化及规律尚不清晰，且缺乏有效的在体可视化分子显像方法实现对三者的实时检测。本课题拟采用可分别与浸润的巨噬细胞、凋亡细胞和新生微血管三个VAP关键成因靶标特异结合的新型分子探针（18F-FEDAA1106、99mTc-Duramycin和99mTc- RGD）及分子显像技术，探测三种分子探针与动脉病变中浸润巨噬细胞、凋亡细胞和新生微血管特异结合后局部的异常分子表达，以及各成因靶标分子表达"信号"在动脉壁上聚集量随时间相互"涨消"的动态变化规律，揭示各关键成因靶标在动脉壁的聚集数量与VAP演进的关系；阐明在体VAP演进中关键成因靶标之间的相互关系和动态变化规律与动脉斑块稳定性的关系；为监测VAP的演进过程提供新型在体"可视化"分子显像技术和实验依据。

急性心脏事件与动脉易损斑块（vulnerable atherosclerotic plaque，VAP）密切相关，有效地鉴别动脉斑块的性质，区分稳定斑块和易损斑块，对VAP的早期发现和及时干预，以及防止和降低急性心脏事件发生有至关重要的意义。应用于VAP研究的检测技术已突破了以往单纯依靠解剖形态学特征的评价，而直接针对与VAP形成相关的关键成因靶标，通过“捕捉”在体成因靶标的异常分子表达，为VAP分子机制的研究创造前提条件。本课题将高效放射性分子探针18F- FDG、99mTc-Duramycin和99mTc-RGD分别引入家兔模型活体内，与腹主动脉斑块处相应VAP关键成因靶标（巨噬细胞、凋亡细胞和新生微血管）特异性结合，通过不同组别在不同时间点腹主动脉部位放射性分布的异常表达及聚集量的动态变化，从分子水平揭示动脉易损斑块中的关键成因靶标的变化，从而间接评估动脉易损斑块的不稳定性，为临床的危险度评估提供一种无创的方法。