Detection of vulnerable atherosclerotic plaque with a novel 18F-labeled Integrin targeted PET imaging agent

使用新型 18F 标记整合素靶向 PET 显像剂检测易损动脉粥样硬化斑块

• 批准号: 9458355
• 负责人: Balaji K. Tamarappoo
• 金额: $ 49.64万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9458355
• 关键词: Detection; vulnerable; atherosclerotic; plaque; novel

ABSTRACT Myocardial infarction and stroke are major causes of morbidity and mortality among patients with cardiovascular disease and a major cause of long-term disability in the United States. Current imaging techniques are primarily used to determine the severity of luminal stenosis resulting from carotid plaque; however, stroke and transient ischemic attack (TIA) are often associated with the rupture of plaques from regions with non-significant luminal stenosis. Accurate identification of these high-risk, rupture-prone plaques may potentially prevent stroke, TIA and myocardial infarction in a significant number of patients. Non-contrast CT and CT angiography (CTA) are capable of quantifying calcium burden, plaque ulceration, and presence of lipid; however, CT uses ionizing radiation and cannot provide further information regarding risk of plaque rupture. Magnetic resonance imaging and angiography (MRI-MRA) can be used for assessment of plaque composition. However, MRI is technically difficult which prevents its large scale implementation for routine clinical use. There is an unmet clinical need for a non- invasive imaging test to accurately identify carotid plaques which are likely to rupture. Our team is developing a noninvasive test for identification of vulnerable plaque with the use of a new 18F labeled compound that can be detected with positron emission tomography (PET) imaging. This tracer has been shown to bind to integrin molecules found on the cell surface of macrophages, smooth muscle cells and endothelial cells, all of which are found in great abundance in vulnerable plaque. As a first step towards using this agent for clinical applications, we propose to demonstrate that carotid plaque uptake of this compound is increased in vulnerable plaque in patients who have had a recent stroke or TIA relative to patients with stable carotid artery plaque who are free of stroke or TIA. Our goal is to develop a noninvasive imaging test that can predict which carotid plaque is vulnerable and at an increased risk of rupture. This will enable physicians to prevent stroke or TIA in these patients by removal of plaque by surgery or carotid artery stenting. Ultimately, this technology may be used to detect vulnerable plaque in other vascular beds including the coronary arteries.

摘要 心肌梗死和中风是患者发病和死亡的主要原因 心血管疾病和长期残疾的主要原因在美国。 目前的成像技术主要用于确定管腔狭窄的严重程度 然而，中风和短暂性脑缺血发作（TIA）通常是由颈动脉斑块引起的。 与来自非显著管腔狭窄区域的斑块破裂相关。 准确识别这些高风险、易破裂的斑块可能会预防中风， TIA和心肌梗死的患者数量可观。非增强CT和CT 血管造影（CTA）能够定量钙负荷、斑块溃疡和存在 然而，CT使用电离辐射，无法提供有关 斑块破裂的风险。可以使用磁共振成像和血管造影（MRI-MRA） 用于评估牙菌斑组成。然而，MRI在技术上是困难的， 用于常规临床使用的大规模实施。有一个未满足的临床需求，非- 侵入性成像测试，以准确识别可能破裂的颈动脉斑块。我们的团队 正在开发一种使用新型18 F识别易损斑块的非侵入性测试 标记的化合物，其可以用正电子发射断层扫描（PET）成像检测。这 示踪剂已显示与巨噬细胞细胞表面上发现的整联蛋白分子结合， 平滑肌细胞和内皮细胞，所有这些都大量存在于 易损斑块作为第一步使用这种代理的临床应用，我们建议 为了证明在不稳定斑块中颈动脉斑块对该化合物的摄取增加， 相对于颈动脉稳定的患者，近期发生卒中或TIA的患者 没有中风或短暂性脑缺血发作的患者。我们的目标是开发一种非侵入性的成像测试， 预测哪些颈动脉斑块是脆弱的，并且破裂的风险增加。这将使 医生通过手术或颈动脉粥样硬化斑块清除来预防这些患者的卒中或TIA 动脉支架术最终，该技术可用于检测其他疾病中的易损斑块。 包括冠状动脉在内的血管床

项目成果

Decrease in LDL-C is associated with decrease in all components of noncalcified plaque on coronary CTA.

LDL-C 的降低与冠状动脉 CTA 上非钙化斑块所有成分的减少相关。

• DOI: 10.1016/j.atherosclerosis.2019.04.201
• 发表时间: 2019
• 期刊: Atherosclerosis
• 影响因子: 5.3
• 作者: Otaki,Yuka;Tamarappoo,Balaji;Cadet,SebastienJ;Doris,Mhairi;Arnson,Yoav;Huynh,PhiT;Gransar,Heidi;Wang,Frances;Hayes,SeanW;Friedman,JohnD;Thomson,Louise;Slomka,Piotr;Dey,Damini;Berman,DanielS
• 通讯作者: Berman,DanielS

Diagnostic Accuracy of Cardiovascular Magnetic Resonance for Cardiac Transplant Rejection: A Meta-Analysis.

心血管磁共振对心脏移植排斥反应的诊断准确性：荟萃分析。

• DOI: 10.1016/j.jcmg.2021.05.008
• 发表时间: 2021
• 期刊: JACC. Cardiovascular imaging
• 作者: Han,Donghee;Miller,RobertJH;Otaki,Yuka;Gransar,Heidi;Kransdorf,Evan;Hamilton,Michelle;Kittelson,Michele;Patel,Jignesh;Kobashigawa,JonA;Thomson,Louise;Berman,Daniel;Tamarappoo,Balaji
• 通讯作者: Tamarappoo,Balaji

Prognostic Value of Computed Tomography-Derived Extracellular Volume in TAVR Patients With Low-Flow Low-Gradient Aortic Stenosis.

• DOI: 10.1016/j.jcmg.2020.07.045
• 发表时间: 2020-12
• 期刊: JACC. Cardiovascular imaging
• 作者: Tamarappoo B;Han D;Tyler J;Chakravarty T;Otaki Y;Miller R;Eisenberg E;Singh S;Shiota T;Siegel R;Stegic J;Salseth T;Cheng W;Dey D;Thomson L;Berman D;Friedman J;Makkar R
• 通讯作者: Makkar R