Imaging Incipient Heart Failure by PET
通过 PET 对早期心力衰竭进行成像
基本信息
- 批准号:10680080
- 负责人:
- 金额:$ 6.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-15 至 2025-09-14
- 项目状态:未结题
- 来源:
- 关键词:AccountingAcetate-CoA LigaseAcetyl Coenzyme AAcidsAnimal ModelBehaviorBiochemical PathwayBiological AssayBiological MarkersBypassCancer DetectionCardiacCardiac MyocytesCardiomyopathiesCatabolismCellsClinicCoenzyme ACoenzyme A LigasesDetectionDiagnosisDiseaseEarly DiagnosisEchocardiographyEffectivenessEnzymesEventFamilyFamily memberFellowshipFluorineFoundationsGoalsHealthHeartHeart DiseasesHeart InjuriesHeart failureHumanImageImpairmentIn VitroIncubatedInterventionIsoproterenolIsotopesKineticsKnock-outKnowledgeLabelMalignant neoplasm of prostateMedicalMembraneMetabolicMetabolismMethodsMitochondriaModalityModelingMusMyocardiumOrganellesPathologicPathway interactionsPatientsPhasePositronPositron-Emission TomographyPreventive carePropionic AcidsReportingResearchRiskRodentRoleSafetySeverity of illnessSurveysSystemTestingTherapeutic InterventionTracerTrainingTranslationsUnited StatesValidationVolatile Fatty Acidsaorta constrictioncancer imagingcardiometabolismcardiovascular healthcareerclinical translationdosimetryexperiencefatty acid metabolismfatty acid oxidationheart damageheart imagingheart metabolismimaging probeimprovedliquid chromatography mass spectrometrylong chain fatty acidmetabolic imagingmolecular imagingmortalitypatient prognosispreventresponsetooluptake
项目摘要
PROJECT SUMMARY
Heart failure represents a major cause of illness and mortality in the United States. Preemptive and preventative
care are the most effective methods for mitigating the severity of this disease. Thus, the early detection of heart
failure is critical to patient prognosis and overall cardiovascular health. The conventional methods for diagnosis
are limited to detection of significant cardiac damage and pathological remodeling. We propose using 2-
[18F]fluoropropionic acid ([18F]FPA) to image the metabolic alterations in fatty acid metabolism which precede
cardiac injury. [18F]FPA-PET is favorably suited for imaging these events and translation to the clinic as: 1)
[18F]FPA-PET has been used for imaging tumors in humans and accumulates in the heart, thereby confirming
its safety and favorable dosimetry, 2) short chain fatty acids, such as [18F]FPA, are preferentially taken up by the
injured heart in response to the impairment in long chain fatty acid oxidation, 3) propionic acid metabolism is
restricted to a single mitochondrial pathway which targets [18F]FPA to this organelle and limits its potential for
degradation. We predict the metabolic alterations that occur during heart failure effectively increase the uptake
and sequestration of [18F]FPA to the myocardium. The metabolic trapping of [18F]FPA is driven by acetyl-CoA
synthetase short chain family 1 (ACSS1), which converts these short chain fatty acids to metabolically active
and membrane impermeable CoA intermediates. ACSS1 expression and activity are upregulated in patients
experiencing heart failure, and many animal models of heart failure. Thus, we hypothesize that [18F]FPA
effectively accumulates in the injured heart and can be applied to image the early manifestations of cardiac
disease which precede irreversible cardiac injury and remodeling. The goals of this fellowship project are to 1)
determine if [18F]FPA can be used to image heart failure, and 2) investigate the role of ACSS1 in accounting for
the cardiac accumulation of [18F]FPA. The successful application of most imaging probes depends on a
comprehensive understanding of the biochemical pathways that these probes report on. In building our
understanding, we can develop precise applications for these tracers to image heart failure, as well as other
disease states. The long-term goals of this project will serve as a foundation for the applicant's independent
research career. These will be facilitated by the technical, conceptual, and practical knowledge that he will gain
over the course of the fellowship training.
项目总结
在美国,心力衰竭是疾病和死亡的主要原因。先发制人和预防性
护理是减轻这种疾病严重程度的最有效方法。因此,心脏的早期检测
失败对患者预后和整体心血管健康至关重要。传统的诊断方法
仅限于检测严重的心脏损伤和病理性重构。我们建议使用2-
[18F]氟丙酸([18F]FPA)成像脂肪酸代谢之前的代谢变化
心脏损伤。[18F]FPA-PET非常适合于对这些事件进行成像,并将其翻译到临床上,如下所示:1)
[18F]FPA-PET已被用于对人体肿瘤进行成像,并在心脏积聚,从而证实
它的安全性和良好的剂量学特性,2)短链脂肪酸,如[18F]FPA,优先被
损伤心脏对长链脂肪酸氧化损伤的反应,3)丙酸代谢
仅限于将[18F]FPA靶向该细胞器的单一线粒体途径,并限制其潜在的
退化。我们预测,在心力衰竭期间发生的代谢变化有效地增加了摄取
并将[18F]FPA隔离到心肌。乙酰辅酶A驱动[18F]FPA的代谢捕获
合成酶短链家族1(ACSS1),它将这些短链脂肪酸转化为具有代谢活性的脂肪酸
和膜不透性CoA中间体。ACSS1在患者体内的表达和活性上调
经历心力衰竭,以及许多心力衰竭的动物模型。因此,我们假设[18F]FPA
有效地积聚在受损心脏中,可用于心脏早期表现的成像
先于不可逆的心脏损伤和重塑的疾病。该奖学金项目的目标是1)
确定[18F]FPA是否可用于心力衰竭的成像,以及2)研究ACSS1在解释
[18F]FPA的心脏蓄积。大多数成像探头的成功应用取决于
全面了解这些探针报告的生化途径。在建设我们的
了解后,我们可以开发这些示踪剂的精确应用程序来成像心力衰竭以及其他
疾病状态。该项目的长期目标将作为申请者独立的
研究生涯。这些将由他将获得的技术、概念和实践知识来促进
在团契训练的过程中。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Juan Arturo Azcona其他文献
Juan Arturo Azcona的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}