炎症和微钙化PET/CT联合显像用于动脉粥样硬化斑块不稳定性的评估

There is still lack of effective probes for atherosclerosis vulnerable plaques detection. Based on the SPECT/CT inflammatory imaging agent 99mTc-MAG3-anti-CD11b-Ab we fabricated in previous study, high signal-to-background ratio and high sensitivity in identifying vulnerable and inflamed atherosclerotic plaques was achieved. We assumed CD11b will be a potential important target for developing PET imaging agent in detecting inflammation in vulnerable atherosclerotic plaques. It’s known that inflammation and micro-calcification correlated tightly in the process of vulnerable plaques, as well as the up-to-date status that 18F-NaF presents high specificity in detecting rupture-prone plaques based on micro-calcification detection. Herein, we aim to fabricate a 64Cu labeled anti-CD11b mediated imaging agent for PET/CT inflammation imaging, together with 18F-NaF mediated micro-calcification PET/CT imaging, to dynamically assess the process of inflammation and micro-calcification and their inter-relationship. This study may provide an insight into understanding the intertwined mechanism of the inflammation and micro-calcification in dynamic process of vulnerable plaques by virtue of non-invasive molecular imaging method. Hopefully, these two combined imaging system may provide a novel strategy for early detecting rupture-prone plaque and its rupture-risk stratification, eventually facilitate to timely diagnosis and intervention of vulnerable atherosclerotic plaques.

动脉粥样硬化易损斑块的PET显像目前仍缺乏有效的显像剂，我们在前期研究中发现99mTc-MAG3-anti-CD11b-Ab 用于斑块部位的炎症反应SPECT显像具有高敏感性和高信噪比，基于此提出“CD11b是研制新型PET炎症显像剂的潜在重要靶标”的假说。结合炎症和微钙化在动脉粥样硬化易损斑块发生发展中的重要作用和相互关联密切的理论基础，以及18F-NaF用于粥样硬化斑块微钙化显像特异性高的研究现状，本项目尝试研制64Cu标记的anti-CD11b-Ab PET炎症显像剂，并联合18F-NaF PET/CT动态评估动脉粥样硬化炎症和微钙化的动态发展过程及相互关联。本项目的完成有望通过无创显像手段深入了解斑块炎症和微钙化动态发展过程和相互作用机制，并为易损斑块检测和危险分层提供新的高敏感性和高特异性评估手段，促进易损斑块的早期诊断和干预。

动脉粥样硬化易损斑块的PET显像目前仍缺乏有效的显像剂，结合炎症和微钙化在动脉粥样硬化易损斑块发生发展中的重要作用和相互关联密切的理论基础，以及18F-NaF用于粥样硬化斑块微钙化显像特异性高的研究现状，我们使用AS小鼠模型，成功制备了具有高纯度、高稳定性、高生物亲和力的Na18F、99mTc-MAG3-HFn（靶向巨噬细胞转铁蛋白）、99mTc-DTPA-HFn（靶向巨噬细胞转铁蛋白）、125I-HF（靶向巨噬细胞转铁蛋白）、99mTc-duramycin（靶向凋亡细胞）、99mTc-Annexin V（靶向凋亡细胞）、99mTc-MAG3-anti-CD11b-Ab（靶向巨噬细胞），对 ApoE-/-基因敲除 AS 易损斑块模型鼠进行活体 SPECT/CT 和 PET/CT 显像，以探讨其用于动脉粥样硬化斑块不稳定性的评估。并通过体外 病理、油红染色以及体外荧光成像进一步验证其对 AS 易损斑块的靶向性。通过以上实验，我们发现通过结合AS相关炎症和微钙化，能更有效地监测AS不稳定斑块。