Molecular Imaging of the ChemR23-Chemerin Axis in Acute Lung Injury
急性肺损伤中 ChemR23-Chemerin 轴的分子成像
基本信息
- 批准号:10441149
- 负责人:
- 金额:$ 5.16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAcute Lung InjuryAcute Respiratory Distress SyndromeAffinityAgonistAlveolarAsthmaAutomobile DrivingBindingBiochemicalBiologicalBiological MarkersBiopsyBronchoalveolar LavageC-terminalCMKLR1 geneCellsChemotactic FactorsChronicClinicalComplexCritical IllnessDendritic CellsDetectionDevelopmentDiseaseEpithelial CellsExhibitsFrightFunctional disorderG-Protein-Coupled ReceptorsGTP-Binding Protein alpha Subunits, GsGasesGoalsHistologicImageImmuneImpairmentIndividualInflammationInflammation MediatorsInflammatoryInflammatory ResponseInjuryKineticsLifeLipopolysaccharidesLungLung diseasesMeasuresMediatingMethodsModificationMonitorNatural Killer CellsNeutrophil InfiltrationNon-Invasive Cancer DetectionOutcomePathogenicityPatientsPeptide HydrolasesPeptidesPhasePhenotypePlasmaPlayPopulationPositron-Emission TomographyPreparationProcessPropertyProteolytic ProcessingPulmonary InflammationQuality of lifeRadiolabeledResearchResolutionRiskSerine ProteaseSerumSiteSpecificityTailTissuesTracerValidationantagonistbasecell motilitychemokine receptorclinical practiceclinical prognosticcontrast imagingdesignextracellularfluorodeoxyglucoseimaging biomarkerimaging probeimmune activationimmunomodulatory therapiesimprovedin vivo imagingindexinginflammatory milieulung injurymacrophagemigrationmolecular imagingmouse modelneutrophilnon-invasive imagingnovelpeptidomimeticspersonalized medicineprecision medicineprognosticprognostic toolprototyperadiotracerreceptorsmoke inhalationuptake
项目摘要
Project Summary
Acute lung injury (ALI), clinically known as acute respiratory distress syndrome (ARDS), is a severe and
potentially life-threatening condition with different sub-phenotypes leading to distinct clinical outcomes. In
particular, patients with non-resolving pulmonary inflammation who survive the acute phase of ARDS are a
subpopulation at increased risk for poor outcomes, including long term lung damage and significantly decreased
quality of life. Therefore, developing strategies to monitor ongoing lung inflammation based on inflammatory
signatures (i.e. specific inflammatory mediators and individual immune cell populations) represents a Precision
Medicine approach, especially relevant given the growing development and applications of immunomodulatory
therapies. Molecular imaging using positron emission tomography (PET) is emerging as a promising non-
invasive approach that can used to visualize inflammatory processes and provide prognostic information. Current
PET tracers, primarily 18F-FDG, for lung inflammation suffer from a lack of specificity and poor kinetics. We
propose developing PET tracers targeting the receptor/chemokine ChemR23/chemerin, a newly established
biomarker for imaging lung inflammation. We have designed two classes of PET tracers, an “active” probe
imaging the expression of ChemR23 and an “activatable” probe imaging the inflammatory-protease bioactivation
of the ChemR23-chemerin axis. Our central hypothesis is that modification of the “active” tracer into an
“activatable” tracer through addition of a cleavable C-terminal tail will enhance the specificity of imaging the
ChemR23-chemerin axis by mimicking the local bioactivation and ultimately uptake of chemerin in the
inflammatory environment. We propose two specific aims: SPECIFIC AIM 1: To synthesize and biologically
characterize active and protease-activatable chemerin-derived radiotracers. SPECIFIC AIM 2: To determine the
biological, biochemical, and histological correlates of ChemR23-targeted PET by “active” and “activatable”
tracers in a mouse model of ALI. Our ultimate goal is to develop bioactivatable PET tracers for precision medicine
imaging of ongoing lung injury and inflammation along the ChemR23-chemerin axis to improve research and
clinical prognostic tools.
项目摘要
急性肺损伤(ALI),临床上称为急性呼吸窘迫综合征(ARDS),是严重的
潜在的威胁生命的条件具有不同的亚表型,导致不同的临床结果。在
特别是,在ARDS的急性阶段生存的非分辨肺部炎症患者是A
以不良预后风险增加的亚种群,包括长期肺损伤,并显着减少
生活质量。因此,制定策略以根据炎症监测正在进行的肺部感染
签名(即特定的炎症介质和个体免疫细胞种群)代表精度
鉴于免疫调节的发展和应用的不断增长,医学方法尤其相关
疗法。使用正电子发射断层扫描(PET)的分子成像正在成为有望的非 -
可视化炎症过程并提供预后信息的侵入性方法。当前的
宠物示踪剂,主要18F-FDG,用于肺部注射的宠物示踪剂缺乏特异性和动力学差。我们
提案开发针对接收器/趋化因子Chemr23/chemerin的宠物示踪剂,这是一种新建立的
用于成像肺部感染的生物标志物。我们设计了两类宠物示踪剂,一个“活跃”证明了
成像ChemR23的表达和“可激活”的探针成像炎症性蛋白酶生物活化
ChemR23-化合物轴的轴。我们的中心假设是将“主动”示踪剂的修改为
通过添加可裂解的C末端尾部,“可激活”示踪剂将增强成像的特异性
通过模仿局部生物活化并最终吸收Chemerin
炎症环境。我们提出了两个具体目标:特定目的1:合成和生物学上
表征活性和蛋白酶 - 可激活化学蛋白衍生的放射性示例。特定目标2:确定
通过“活跃”和“可启动”靶向ChemR23靶向PET的生物学,生化和组织学相关性
Ali小鼠模型中的示踪剂。我们的最终目标是开发精密医学的可生物活化宠物示踪剂
沿ChemR23-化合物轴的持续肺损伤和炎症的成像,以改善研究和
临床预后工具。
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 }}
Philip Zachary Mannes其他文献
Philip Zachary Mannes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 }}
{{ truncateString('Philip Zachary Mannes', 18)}}的其他基金
Molecular Imaging of the ChemR23-Chemerin Axis in Acute Lung Injury
急性肺损伤中 ChemR23-Chemerin 轴的分子成像
- 批准号:
10228139 - 财政年份:2021
- 资助金额:
$ 5.16万 - 项目类别:
Molecular Imaging of the ChemR23-Chemerin Axis in Acute Lung Injury
急性肺损伤中 ChemR23-Chemerin 轴的分子成像
- 批准号:
10625359 - 财政年份:2021
- 资助金额:
$ 5.16万 - 项目类别:
相似国自然基金
circRNA-Hace1通过调控RNA结合蛋白G3BP2对甲型流感病毒致急性呼吸窘迫综合征肺损伤的保护作用及机制研究
- 批准号:82000023
- 批准年份:2020
- 资助金额:24 万元
- 项目类别:青年科学基金项目
阿魏酸、槲皮素、甘草酸组合物拮抗禽流感病毒H5N1血凝素蛋白介导急性肺损伤的药理学作用及机制研究
- 批准号:81902019
- 批准年份:2019
- 资助金额:20.0 万元
- 项目类别:青年科学基金项目
IL-33/ST2通路调控树突状细胞诱导Th17细胞分化参与ARDS时肺部炎症反应的机制研究
- 批准号:81900079
- 批准年份:2019
- 资助金额:20.0 万元
- 项目类别:青年科学基金项目
IL-17B在急性肺损伤中的诊疗价值及免疫机制研究
- 批准号:81802079
- 批准年份:2018
- 资助金额:21.0 万元
- 项目类别:青年科学基金项目
脂肪组织源循环外泌体通过miR221/ETS1调控肺微血管内皮细胞屏障稳态在ARDS肥胖悖论中的作用及机制研究
- 批准号:81800083
- 批准年份:2018
- 资助金额:21.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Patient Ventilator Asynchrony in Critically Ill Children
危重儿童患者呼吸机异步
- 批准号:
10657157 - 财政年份:2023
- 资助金额:
$ 5.16万 - 项目类别:
Red blood cell ATP export and transfusion in sepsis
脓毒症中红细胞 ATP 输出和输血
- 批准号:
10584768 - 财政年份:2023
- 资助金额:
$ 5.16万 - 项目类别:
Understanding and targeting fibroblast activation in influenza-triggered lung inflammation and post-viral disease
了解和靶向流感引发的肺部炎症和病毒后疾病中的成纤维细胞激活
- 批准号:
10717809 - 财政年份:2023
- 资助金额:
$ 5.16万 - 项目类别:
The role of epigenetic regulator UHRF1 in stability of induced regulatory T-cell function during influenza A virus-induced lung injury
表观遗传调节因子 UHRF1 在甲型流感病毒诱导的肺损伤过程中诱导调节 T 细胞功能稳定性中的作用
- 批准号:
10389878 - 财政年份:2023
- 资助金额:
$ 5.16万 - 项目类别: