Ga68-DOTATATE PET imaging of plaque inflammation

斑块炎症的 Ga68-DOTATATE PET 成像

• 批准号: 9914121
• 负责人: Zahi A. Fayad
• 金额: $ 79.22万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9914121
• 关键词: Advocate; Aftercare; Algorithms; Animal Model; Animals; Arterial Fatty Streak; Atherosclerosis; Autoradiography; Biological Markers; Blood; Blood Circulation; Blood Vessels; Cancer Patient; Cardiovascular Diseases; Carotid Arteries; Carotid Endarterectomy; Cell physiology; Cells; Clinical; Clinical Trials; Coronary; Coronary Arteriosclerosis; Coronary artery; Detection; Development; Diagnosis; Discrimination; Disease; Disease Progression; Event; Exposure to; FDA approved; Flow Cytometry; Fluorescence; Future; Gene Expression Profiling; Goals; Gold; Hypoxia; Image; Imaging Techniques; Immunohistochemistry; Inflammation; Inflammatory; Injections; Ionizing radiation; Laboratories; Low-Density Lipoproteins; Magnetic Resonance Imaging; Morbidity - disease rate; Motion; Mus; Myocardial; Myocardial Infarction; Neuroendocrine Tumors; Neurosecretory Systems; Oryctolagus cuniculus; PET/CT scan; Pathogenesis; Patients; Positron-Emission Tomography; Predictive Value; Receptor Cell; Recording of previous events; Regimen; Retrospective Studies; Risk Factors; Role; Rupture; SSTR2 gene; Schedule; Specificity; Stroke; Therapeutic; Time; Tracer; Translating; Work; X-Ray Computed Tomography; acute coronary syndrome; atherogenesis; cardiovascular disorder risk; cardiovascular risk factor; cell type; clinical imaging; clinically relevant; density; experimental study; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; high risk; human subject; imaging biomarker; improved; in vivo; in vivo imaging; innovation; macrophage; microPET; mortality; non-invasive imaging; novel; overexpression; personalized medicine; pre-clinical; prospective; somatostatin receptor 2; uptake

PROJECT SUMMARY Atherosclerotic cardiovascular disease (CVD) is the main cause of morbidity and mortality worldwide. Among the several cell types and processes involved in atherogenesis, the role of macrophages in the formation of high-risk plaques is well established and characterized. The past 15 years have seen tremendous efforts to develop and validate non-invasive imaging to quantify plaque macrophages and improve CVD patients management. Even nowadays, the role of imaging continues to be advocated to better define atherosclerosis and to improve assessment of therapeutic regimens.18F-FDG PET is a non-invasive, translational imaging technique widely used and validated to quantify plaque macrophages in vivo. However, vascular 18F-FDG PET still carries several important limitations. For example, while 18F-FDG vessel wall accumulation has been consistently correlated to plaque inflammation, uptake is not specific for macrophages, and can be influenced by other factors, such as hypoxia and vascular density. To overcome these limitations, several novel PET tracers more specific to unique molecules, receptors and cells involved in plaque inflammation are currently being investigated. 68Ga-DOTATATE is a novel PET tracer, recently approved by the FDA to improve detection of somatostatin receptor 2 (SSTR2) -positive neuroendocrine tumors. SSTR2s are also overexpressed on activated plaque macrophages. Preliminary studies have found 68Ga-DOTATATE to accumulate in macrophage-rich plaques in atherosclerotic mice. Retrospective analyses have confirmed accumulation in the atherosclerotic vessel wall in cancer patients. Building on these previous studies, we propose to establish and translate 68Ga-DOTATATE as a specific, non-invasive marker of atherosclerotic plaque macrophages. In parallel with mechanistic studies in atherosclerotic mice on PET/CT, we will translate 68Ga-DOTATATE PET on a combined PET/MR scanner in large animals (rabbits) and patients with coronary atherosclerosis. 68Ga-DOTATATE may be particularly useful when imaging this challenging vascular territory, where 18F-FDG PET is notoriously difficult because of the strong, non-specific myocardial background uptake. Our laboratory is deeply involved in translational PET/MRI for imaging of coronary atherosclerosis, by developing innovative motion correction, partial volume correction algorithms and dynamic PET imaging to improve PET tracers uptake in the coronary arteries (R01 HL071021, PI Fayad). We anticipate that establishing 68Ga-DOTATATE PET may allow improving the management of CVD patients, the quantitative assessment of novel anti-atherosclerotic compounds, and, in the future, prove useful to improve diagnosis of other CVD conditions. While beyond the scope of our work, this proposal is the basis for more extensive, prospective clinical trials investigating the predictive value of 68Ga-DOTATATE PET and other promising imaging markers for CVD events.

项目概要 动脉粥样硬化性心血管疾病（CVD）是全世界发病和死亡的主要原因。之中 参与动脉粥样硬化形成的几种细胞类型和过程，巨噬细胞在动脉粥样硬化形成中的作用 高风险斑块已被充分确定并具有特征。过去15年，我们付出了巨大的努力 开发和验证非侵入性成像以量化斑块巨噬细胞并改善 CVD 患者的状况 管理。即使在今天，影像学在更好地定义动脉粥样硬化方面的作用仍然被提倡 并改善治疗方案的评估。18F-FDG PET 是一种非侵入性平移成像 广泛使用和验证的技术可量化体内斑块巨噬细胞。然而，血管 18F-FDG PET 仍然存在一些重要的局限性。例如，虽然 18F-FDG 血管壁积聚已 与斑块炎症始终相关，摄取对于巨噬细胞来说不是特异性的，并且可能受到影响 受其他因素影响，例如缺氧和血管密度。为了克服这些限制，几种新型 PET 目前，针对参与斑块炎症的独特分子、受体和细胞更具特异性的示踪剂 正在接受调查。 68Ga-DOTATATE 是一种新型 PET 示踪剂，最近获得 FDA 批准，可改善 检测生长抑素受体 2 (SSTR2) 阳性神经内分泌肿瘤。 SSTR2 还 在活化的斑块巨噬细胞上过度表达。初步研究发现 68Ga-DOTATATE 积聚在动脉粥样硬化小鼠富含巨噬细胞的斑块中。回顾性分析证实 癌症患者的动脉粥样硬化血管壁中积聚。基于这些先前的研究，我们 提议建立并转化 68Ga-DOTATATE 作为动脉粥样硬化的特异性、非侵入性标记物 斑块巨噬细胞。在 PET/CT 上对动脉粥样硬化小鼠进行机制研究的同时，我们将翻译 大型动物（兔子）和冠状动脉患者的 68Ga-DOTATATE PET 联合 PET/MR 扫描仪 动脉粥样硬化。在对这一具有挑战性的血管区域进行成像时，68Ga-DOTATATE 可能特别有用， 其中 18F-FDG PET 非常困难，因为心肌背景摄取很强，非特异性。 我们的实验室深入参与用于冠状动脉粥样硬化成像的平移 PET/MRI 领域， 开发创新的运动校正、部分容积校正算法和动态 PET 成像，以 改善冠状动脉中 PET 示踪剂的摄取（R01 HL071021，PI Fayad）。我们预计 建立 68Ga-DOTATATE PET 可以改善 CVD 患者的管理，定量 评估新型抗动脉粥样硬化化合物，并在未来证明有助于改善诊断 其他 CVD 条件。虽然超出了我们的工作范围，但该提案是更广泛的基础， 前瞻性临床试验调查 68Ga-DOTATATE PET 和其他有前途的预测价值 CVD 事件的影像标记。

项目成果

Sodium Fluoride PET and Aortic Bioprosthetic Valve Degeneration: Implications for Patient Diagnosis, Management, and Treatment.

氟化钠 PET 和主动脉生物瓣膜变性：对患者诊断、管理和治疗的影响。

• 发表时间: 2019
• 影响因子: 24
• 作者: Fayad, Zahi A;Calcagno, Claudia
• 通讯作者: Calcagno, Claudia

Pericoronary and periaortic adipose tissue density are associated with inflammatory disease activity in Takayasu arteritis and atherosclerosis.

冠状动脉周围和主动脉周围脂肪组织密度与大动脉炎和动脉粥样硬化的炎症活动相关。

• 发表时间: 2021-09
• 作者: Wall, Christopher;Huang, Yuan;Le, Elizabeth P V;Ćorović, Andrej;Uy, Christopher P;Gopalan, Deepa;Ma, Chuoxin;Manavaki, Roido;Fryer, Tim D;Aloj, Luigi;Graves, Martin J;Tombetti, Enrico;Ariff, Ben;Bambrough, Paul;Hoole, Stephen P;Rusk, Rosema
• 通讯作者: Rusk, Rosema

Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis.

大血管炎和动脉粥样硬化患者炎症的生长抑素受体 PET/MR 成像。

• 发表时间: 2023-01-31
• 影响因子: 24
• 作者: Ćorović, Andrej;Wall, Christopher;Nus, Meritxell;Gopalan, Deepa;Huang, Yuan;Imaz, Maria;Zulcinski, Michal;Peverelli, Marta;Uryga, Anna;Lambert, Jordi;Bressan, Dario;Maughan, Robert T;Pericleous, Charis;Dubash, Suraiya;Jordan, Natasha;Jayne
• 通讯作者: Jayne