Imaging High-Risk Atherothrombosis Using a Novel Fibrin-Binding Positron Emission Tomography Probe.
Imaging High-Risk Atherothrombosis Using a Novel Fibrin-Binding Positron Emission Tomography Probe.
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DOI：
10.1161/strokeaha.121.035638
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发表时间：
2022-03
期刊：
影响因子：
8.3
通讯作者：
Ay I
中科院分区：
文献类型：
--
作者：
Izquierdo-Garcia D;Diyabalanage H;Ramsay IA;Rotile NJ;Mauskapf A;Choi JK;Witzel T;Humblet V;Jaffer FA;Brownell AL;Tawakol A;Catana C;Conrad MF;Caravan P;Ay I
高危动脉粥样硬化是心血管事件的潜在病因，但确定特定患者人群的直接风险仍然具有挑战性。在这里，我们使用兔模型动脉粥样硬化斑块破裂和人颈动脉内膜切除标本来描述分子纤维蛋白成像作为一种工具来识别血栓斑块的潜力。使用高胆固醇饮食和主动脉球囊损伤诱导家兔动脉粥样硬化斑块（N=13）。在一组家兔（n=9）中使用药理学触发以诱导斑块破裂。根据大体病理学（金标准）将动物分为血栓性和非血栓性斑块组。所有动物均注射新型纤维蛋白特异性探针68 Ga-CM 246，90分钟后进行PET/MR成像。使用组织与背景（背部肌肉）比率（TBR）和标准化摄取值（SUV）在PET图像上定量68 Ga-CM 246。血栓组的TBR和SUV均显著高于非血栓组（p<0.05）。腹主动脉的离体PET和放射自显影与体内PET测量呈正相关。通过68 Ga-CM 246 PET鉴定的斑块破裂与大体病理学评估一致（85%）。在从经历选择性颈动脉内膜切除术的患者（N=12）获得的离体手术样本中，与D-半胱氨酸非结合对照探针相比，68 Ga-CM 246显示出显著更高的与颈动脉斑块的结合。我们证明，使用68 Ga-CM 246的分子纤维蛋白PET成像可能是诊断实验性和临床动脉粥样硬化血栓形成的有用工具。基于我们使用人颈动脉斑块标本的初步结果，体内分子成像研究有必要测试68 Ga-CM 246 PET作为动脉粥样硬化患者风险分层的工具。
High-risk atherosclerosis is an underlying etiology in cardiovascular events, yet identifying the specific patient population at immediate risk is still challenging. Here, we used a rabbit model of atherosclerotic plaque rupture and human carotid endarterectomy specimens to describe the potential of molecular fibrin imaging as a tool to identify thrombotic plaques. Atherosclerotic plaques in rabbits were induced using a high-cholesterol diet and aortic balloon injury (N=13). Pharmacological triggering was used in a group of rabbits (n=9) to induce plaque disruption. Animals were grouped into thrombotic and non-thrombotic plaque groups based on gross pathology (gold standard). All animals were injected with a novel fibrin-specific probe 68Ga-CM246 followed by PET/MR imaging 90 minutes later. 68Ga-CM246 was quantified on the PET images using tissue-to-background (back muscle) ratios (TBR) and standardized uptake value (SUV). Both TBR and SUV were significantly higher in the thrombotic vs. non-thrombotic group (p<0.05). Ex vivo PET and autoradiography of the abdominal aorta correlated positively with in vivo PET measurements. Plaque disruption identified by 68Ga-CM246 PET agreed with gross pathology assessment (85%). In ex vivo surgical specimens obtained from patients undergoing elective carotid endarterectomy (N=12), 68Ga-CM246 showed significantly higher binding to carotid plaques compared to a D-cysteine non-binding control probe. We demonstrated that molecular fibrin PET imaging using 68Ga-CM246 could be a useful tool to diagnose experimental and clinical atherothrombosis. Based on our initial results using human carotid plaque specimens, in vivo molecular imaging studies are warranted to test 68Ga-CM246 PET as a tool to stratify risk in atherosclerotic patients.
影响因子：
0.9
作者：
Ciesienski, Katie L;Caravan, Peter
通讯作者：
Caravan, Peter
影响因子：
15
作者：
Uppal, Ritika;Ciesienski, Kate L.;Chonde, Daniel B.;Loving, Galen S.;Caravan, Peter
通讯作者：
Caravan, Peter