Myocardial blood flow quantitation with the novel PET F-18 Fluripidaz imaging tracer

使用新型 PET F-18 Fluripidaz 成像示踪剂进行心肌血流定量

• 批准号: 9047781
• 负责人: Jamshid Maddahi
• 金额: $ 49.96万
• 依托单位: SYNTERMED, INC,
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9047781
• 关键词: Address; Affect; Algorithms; American; American Heart Association; Ammonia; Angiography; Award; Blood flow; Cardiac; Cause of Death; Chloride Ion; Chlorides; Clinical; Complex; Coronary; Coronary Arteriosclerosis; Coronary Circulation; Coronary artery; Coronary heart disease; Cyclotrons; Databases; Decision Support Systems; Defect; Detection; Developed Countries; Diagnosis; Diagnostic; Disease; Dose; Early Diagnosis; Enrollment; Evaluation; Evaluation Studies; Exercise; Female; Goals; Grant; Half-Life; Heart Diseases; Image; Imaging Techniques; Injection of therapeutic agent; Kinetics; Label; Left; Left Ventricular Ejection Fraction; Measurement; Measures; Medical Imaging; Methods; Mitochondria; Mitochondrial Proteins; Modeling; Myocardial; Myocardial perfusion; Myocardium; Outcomes Research; Output; Patient Care; Patient-Focused Outcomes; Patients; Perfusion; Phase; Phase III Clinical Trials; Positron-Emission Tomography; Prevention; Procedures; Process; Protocols documentation; Publishing; Quality Control; Radioactive; Regional Perfusion; Reporting; Research Project Grants; Research Proposals; Residual state; Resolution; Rest; Sensitivity and Specificity; Small Business Innovation Research Grant; Specificity; Stress; Stroke; Structure; System; Technetium 99m; Time; Tracer; United States; Update; Ventricular; Visual; Water; analog; attenuation; base; cardiovascular visualization; cost; diagnostic accuracy; imaging agent; improved; inhibitor/antagonist; innovation; male; mortality; natural language; novel; preclinical study; programs; public health relevance; single photon emission computed tomography; statistics; temporal measurement; treadmill

 DESCRIPTION (provided by applicant): Myocardial blood flow quantitation with the novel F-18 Flurpiridaz PET imaging tracer PROECT SUMMARY Coronary artery disease (CAD) is the single largest cause of death in the United States. Prevention, early diagnosis, and treatment of CAD are essential to reduce the mortality. Noninvasive assessments of regional myocardial blood flow at rest and during stress have proved valuable for early diagnosis of CAD. These assessments can be with a radioactive-labeled myocardial perfusion imaging (MPI) agent using Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET), Flurpiridaz F-18 is a novel, new PET myocaridal perfusion imaging (MPI) agent labeled with 18F. This agent is a structural analog of pyridaben, a known mitochondrial complex 1 (MC-1) inhibitor. As mitochondria constitute 20 to 30% of the myocardial intracellular volume, molecules that target mitochondrial proteins will be enriched and retained selectively in the myocardium. In pre-clinical studies, flurpiridaz has shown a higher first pass extraction fraction than Tl-201 and Tc-99m-sestamibi at high flow rates. Thus, flurpiridaz can provide the opportunity to perform myocardial perfusion imaging with the improved resolution and quantification afforded by PET. PET has several technical advantages over SPECT including: 1) routine measured attenuation correction, which decreases the number of false-positives, thereby increasing specificity; 2) high spatial and contrast resolution that allows for improved detection of small perfusion defects which decreases the number of false-negatives, thereby increasing sensitivity; and 3) high temporal resolution that allows fast dynamic imaging of tracer kinetics. The latter makes absolute quantification of MBF possible, which has been shown to improve sensitivity for detection of multi-vessel disease and evaluation of conditions that diffusely affect coronary circulation. Flurpiridaz also could provide improved clinical utility and ease of use because of the longer half-life (109 minutes) of an 18 F-based agent compared to current PET MPI agents (82rubidium (Rb-82) chloride, 13nitrogen (N-13) ammonia, and 15oxygen (O-15) water) that makes delivery of unit doses from regional cyclotrons quite feasible which could not be achieved with the current shorter half-live agents. There is a need to optimize the acquisition and processing protocols in order to take full advantage of this "ideal" MPI agent. The clinical and technical research project proposed in this SBIR submission will address this optimization for the flurpiridaz imaging agent. This Phase II submission is following the nearly completed SBIR Phase I grant 1R43HL123069-01 which was awarded on June 24, 2014. Our long-term objective for this project is to improve patient care and outcomes through increased diagnostic accuracy of coronary heart disease (CHD), maximize clinical diagnostic confidence, and reduce costs by: 1) optimizing the method for flow calculation, 2) establishing quality control procedures and output for evaluation of the study, 3) standardizing the acquisition and processing protocols for Flurpiridaz F-18, 4) developing both relative and absolute quantitation, plus measurements of myocardial blood flow (MBF) and coronary flow reserve (CFR) using the novel new cardiac imaging agent Flurpiridaz F-18, 5) developing an innovative Decision Support System (DSS) system as part of the relative quantitation which will drive an automatic, structured, natural language reporting system thereby increasing clinical confidence and reducing time/cost, and 6) maximizing the availability of these benefits by incorporating all of this into a widely utilized and widely available commercial product, the Emory Cardiac Toolbox(tm) (ECTb).

 描述（由申请人提供）：使用新型F-18氟吡达兹PET成像示踪剂进行心肌血流定量PROECT总结冠状动脉疾病（CAD）是美国最大的单一死亡原因。预防、早期诊断和治疗冠心病是降低死亡率的关键。无创性评估局部心肌血流在休息和在应力已被证明是有价值的CAD的早期诊断。这些评估可以使用放射性标记的心肌灌注成像（MPI）试剂，使用单光子发射计算机断层扫描（SPECT）或正电子发射断层扫描（PET），氟吡达兹F-18是一种新型的18 F标记的PET心肌灌注成像（MPI）试剂。该药剂是哒螨灵的结构类似物，哒螨灵是一种已知的线粒体复合物1（MC-1）抑制剂。由于线粒体占心肌细胞内体积的20 - 30%，靶向线粒体蛋白的分子将被富集并选择性地保留在心肌中。在临床前研究中，在高流速下，氟吡达兹显示出比Tl-201和Tc-99 m-sestamibi更高的首过提取分数。因此，氟吡达兹可以提供进行心肌灌注成像的机会，其具有由PET提供的改进的分辨率和定量。 PET相对于SPECT具有若干技术优势，包括：1）常规测量衰减校正，其减少假阳性的数量，从而增加特异性; 2）高空间和对比度分辨率，其允许改进小灌注缺陷的检测，其减少假阴性的数量，从而增加灵敏度;以及3）高时间分辨率，其允许示踪剂动力学的快速动态成像。后者使得MBF的绝对定量成为可能，这已被证明可以提高检测多血管疾病和评估弥漫性影响冠状动脉循环的条件的灵敏度。氟吡达兹还可以提供改善的临床效用， 易于使用，因为与目前的PET MPI试剂（82氯化铷（Rb-82）、13氮（N-13）氨和15氧（O-15）水）相比，基于18F的试剂的半衰期更长（109分钟），这使得从区域回旋加速器递送单位剂量非常可行，而这是目前较短半衰期的试剂无法实现的。有必要优化的采集和处理协议，以充分利用这个“理想的”MPI代理。本次SBIR申报中提出的临床和技术研究项目将解决氟吡达兹显像剂的优化问题。 本第二阶段申报如下 即将完成的SBIR第一阶段拨款1 R43 HL 123069 -01于2014年6月24日授予。我们对该项目的长期目标是通过提高冠心病（CHD）诊断准确性来改善患者护理和结局，最大限度地提高临床诊断信心，并通过以下方式降低成本：1）优化流量计算方法，2）建立质量控制程序和研究评价输出，3）标准化采集 和处理方案，4）开发相对和绝对定量，以及使用新型心脏成像剂Flurpiridaz F-18测量心肌血流量（MBF）和冠状动脉血流储备（CFR），5）开发创新的决策支持系统（DSS）系统作为相对定量的一部分，自然语言报告系统，从而增加临床置信度并减少时间/成本，以及6）通过将所有这些结合到广泛使用和广泛可用的商业产品EmoryCardiacardialTM（ECTb）中来最大化这些益处的可用性。