Real time imaging of immune cells and glutamate dynamics by PET and metabolic MRI

通过 PET 和代谢 MRI 对免疫细胞和谷氨酸动态进行实时成像

基本信息

  • 批准号:
    10894490
  • 负责人:
  • 金额:
    $ 24.9万
  • 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:
    2023-09-21 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT Activation of immune cells plays a critical role in initiation and progression of multiple sclerosis (MS), leading to progressive neurodegeneration of the central nervous system (CNS). While glutamate imbalance has been described in MS brains and has been proposed to contribute to axonal damage and tissue destruction, the relationships between glutamate dynamics and immune activation during disease progression remain unclear. Presently, the lack of clinically available noninvasive imaging methods to detect immune cells and glutamate metabolism limits our understanding of MS pathogenesis and monitoring of responses to therapies. Recent development of radiotracers for positron emission tomography (PET) have shown great potential for detection of cells from the immune system and for imaging glutamate reuptake by astroglial excitatory amino acid transporter-2 (EAAT2). Specifically, 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG) enables the detection of activated T-cells in inflammatory diseases and cancer models. [18F]Fluoro- fluorenylaspartyl amide ([18F]FFAA) has demonstrated the ability to measure EAAT2 activity in the CNS. Hyperpolarized 13C magnetic resonance spectroscopic imaging (HP 13C MRSI) is an emerging imaging technique which measures enzymatic reactions in vivo in real-time. HP 13C pyruvate has been shown to detect highly glycolytic cells from the innate immune system in peripheral and CNS inflammation models. Recently, pyruvate labelled on the second carbon position, [2-13C]pyruvate, provided a new way to monitor glutamate production in the human brain. This project proposes to validate these innovative noninvasive PET and MR methods to provide a new way to investigate the relationships between innate and adaptive immune responses and glutamate dynamics in preclinical MS models. The mentored phase of this project will develop and validate new neuroimaging technologies: Aim 1 will investigate the potential of [18F]F-AraG and [18F]FFAA PET imaging to visualize activated T-cells and glutamate reuptake during disease progression. Aim 2 will develop and validate HP [2-13C]pyruvate as a method to simultaneously detect pro-inflammatory innate immune cells and determine real-time brain glutamate production. The independent phase of this project will build on these initial results and Aim 3 will evaluate the potential of this multimodal PET and MRI approach to monitor immune responses, glutamate production, and astrocyte functions following therapy. Central to the success of this proposal, Dr. Guglielmetti will have the support and guidance from an established group of experts in neuroimaging, particularly HP 13C MR technology (Dr. Myriam Chaumeil and Dr. Peder Larson) and PET imaging (Dr. Henry VanBrocklin) as well as in neuroimmunology and MS (Dr. Ari Green and Dr. Zamvil), providing her with the necessary skillsets to embark on a career as an independent scientist.
摘要

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 }}

Caroline Guglielmetti其他文献

Caroline Guglielmetti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('Caroline Guglielmetti', 18)}}的其他基金

Real time imaging of immune cells and glutamate dynamics by PET and metabolic MRI
通过 PET 和代谢 MRI 对免疫细胞和谷氨酸动态进行实时成像
  • 批准号:
    10371637
  • 财政年份:
    2022
  • 资助金额:
    $ 24.9万
  • 项目类别:
Real time imaging of immune cells and glutamate dynamics by PET and metabolic MRI
通过 PET 和代谢 MRI 对免疫细胞和谷氨酸动态进行实时成像
  • 批准号:
    10678827
  • 财政年份:
    2022
  • 资助金额:
    $ 24.9万
  • 项目类别:

相似海外基金

Amyotrophic Lateral Sclerosis: treating the circuit behind the disease
肌萎缩侧索硬化症:治疗疾病背后的回路
  • 批准号:
    MR/Y014901/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.9万
  • 项目类别:
    Research Grant
Dysregulation of RNA processing as a driver of motor neuron dysfunction in Amyotrophic Lateral Sclerosis
RNA 加工失调是肌萎缩侧索硬化症运动神经元功能障碍的驱动因素
  • 批准号:
    MR/Y014286/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.9万
  • 项目类别:
    Research Grant
Fasciculation IN Amyotrophic Lateral Sclerosis Using MUMRI (FINALSUM)
使用 MUMRI 治疗肌萎缩侧索硬化症的肌束颤动 (FINALSUM)
  • 批准号:
    MR/Y503502/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.9万
  • 项目类别:
    Research Grant
I-Corps: Developing A Blood-Based Biomarker for the Detection and Monitoring of Amyotrophic Lateral Sclerosis
I-Corps:开发一种基于血液的生物标志物,用于检测和监测肌萎缩侧索硬化症
  • 批准号:
    2317745
  • 财政年份:
    2023
  • 资助金额:
    $ 24.9万
  • 项目类别:
    Standard Grant
Targeted immunotherapy for amyotrophic lateral sclerosis and frontotemporal dementia
肌萎缩侧索硬化症和额颞叶痴呆的靶向免疫治疗
  • 批准号:
    10759808
  • 财政年份:
    2023
  • 资助金额:
    $ 24.9万
  • 项目类别:
Resolving the Role of Neuronal STING in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
解决神经元 STING 在肌萎缩侧索硬化症和额颞叶痴呆中的作用
  • 批准号:
    10606865
  • 财政年份:
    2023
  • 资助金额:
    $ 24.9万
  • 项目类别:
Development of CM-CS1 CAR Treg to Treat Amyotrophic Lateral Sclerosis (ALS)
开发 CM-CS1 CAR Treg 治疗肌萎缩侧索硬化症 (ALS)
  • 批准号:
    10696512
  • 财政年份:
    2023
  • 资助金额:
    $ 24.9万
  • 项目类别:
Metrics for Brain Controlled Communication: A comprehensive review of clinical outcome assessments for communication brain computer interfaces in amyotrophic lateral sclerosis
脑控制通信指标:肌萎缩侧索硬化症通信脑机接口临床结果评估的全面综述
  • 批准号:
    10848139
  • 财政年份:
    2023
  • 资助金额:
    $ 24.9万
  • 项目类别:
The biochemical stratification of amyotrophic lateral sclerosis
肌萎缩侧索硬化症的生化分层
  • 批准号:
    MR/Y001095/1
  • 财政年份:
    2023
  • 资助金额:
    $ 24.9万
  • 项目类别:
    Fellowship
The Gut Microbiota as a Contributor to Sexual Dimorphism in Amyotrophic Lateral Sclerosis
肠道微生物群是肌萎缩侧索硬化症性别二态性的一个促成因素
  • 批准号:
    488892
  • 财政年份:
    2023
  • 资助金额:
    $ 24.9万
  • 项目类别:
    Operating Grants
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了