Clinical translation of targeted intracoronary imaging for inflammatory activity

炎症活动性靶向冠状动脉内成像的临床转化

• 批准号: 10669761
• 负责人: Farouc Amin Jaffer
• 金额: $ 77.13万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-22 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669761
• 关键词: Amendment; Animal Model; Apolipoprotein E; Arterial Fatty Streak; Atherosclerosis; Attenuated; Cardiac Catheterization Procedures; Carotid Endarterectomy; Cathepsins; Catheters; Cause of Death; Cells; Clinical; Clinical Research; Coronary; Coronary Arteriosclerosis; Coronary Thrombosis; Coronary artery; Coronary heart disease; Development; Devices; Diagnosis; Disease Management; Dose; Endothelium; Enzymes; Excision; Family suidae; Fiber; Fluorescence; Fluorescence Microscopy; Grant; Hemorrhage; Histology; Hour; Human; Image; Imaging Device; Imaging Techniques; Imaging technology; Immunohistochemistry; Inferior; Inflammation; Inflammatory; Injections; Intervention; Intravenous; Knowledge; Laboratories; Macrophage; Malignant Neoplasms; Mediating; Mediator; Methodology; Microanatomy; Molecular; Morbidity - disease rate; Multimodal Imaging; Mus; Myocardial Infarction; Near-infrared optical imaging; Operative Surgical Procedures; Optical Coherence Tomography; Oryctolagus cuniculus; Outcome; Oxidative Stress; Pathogenesis; Patients; Peptide Hydrolases; Pharmaceutical Preparations; Play; Process; RNA; Randomized; Reporting; Reproducibility; Research; Risk; Role; Safety; Saline; Severity of illness; Signal Transduction; Specimen; Stents; Structure; Subgroup; System; Technology; Testing; Three-Dimensional Image; Time; Transcript; Translating; Vascularization; Visualization; Work; acute coronary syndrome; advanced disease; atherogenesis; clinical imaging; clinical translation; coronary plaque; design; detection platform; digital; dosage; drug development; first-in-human; follow-up; high resolution imaging; imaging agent; imaging system; improved; in vivo; individual patient; inflammatory marker; innovation; intravital microscopy; mortality; multimodality; novel; optical spectra; percutaneous coronary intervention; pharmacologic; pre-clinical; prevent; progression risk; synergism; targeted agent; targeted imaging; thrombogenesis; tool

Inflammatory activity plays a major role in the development and progression of coronary artery disease (CAD), the major cause of mortality in the US and around the world. Until now, there has been no way to visualize and quantify coronary inflammation with the precision required to impact patient management. There is an opportunity for this capability gap to change, as a new clinical near-infrared fluorescence (NIRF) imaging agent called LUM015 has recently been introduced for cancer applications. LUM015 fluoresces following active cathepsin cleavage and thus appears promising as a highly specific targeted agent for inflammatory activity in atherosclerosis, as cathepsins are key mediators of plaque progression and coronary thrombosis risk. In this grant, we propose to investigate a first-in-human use of LUM015 NIRF for intracoronary CAD assessment. We will accomplish this objective by developing and clinically validating a multimodality imaging system and catheter that simultaneously obtains co-localized, intracoronary optical coherence tomography (OCT) images of lesional microanatomy and LUM015 NIRF to evaluate cathepsin-mediated plaque inflammatory activity. This technology will be clinically translated by investigating the targeting profile and dosing parameters for LUM015 in animal models of atherosclerosis and in humans undergoing carotid endarterectomy (Aim 1). Technology will be developed to spectrally unmix LUM015 NIRF from NIR autofluorescence (NIRAF) that is prevalent in advanced CAD (Aim 2.1). We also will advance NIRF-OCT technology by creating an innovative two-fiber catheter/rotary junction that removes fiber autofluorescence background. The resultant increase in LUM015 NIRF sensitivity will allow the time between injection and imaging to be minimized, which is important to capture many patients undergoing cardiac catheterization (Aim 2.2). The new catheter will also improve OCT image quality, which is inferior in current multimodality systems. After completion of Aims 1 and 2, the intravascular LUM015 NIRF-OCT technology will be tested in patients undergoing cardiac catheterization to show that NIRF- OCT can predict CAD severity (Aim 3). By establishing a new clinical imaging methodology for evaluating coronary microstructure and inflammatory activity in vivo, this work will have a major impact on CAD research, drug development, and personalized CAD management aimed at improving clinical outcomes.

炎症活动在冠状动脉疾病（CAD）的发生和进展中起着重要作用，