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

> **NIH NIH R00** · WASHINGTON UNIVERSITY · 2024 · $239,509

## Abstract

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.

## Key facts

- **NIH application ID:** 10933007
- **Project number:** 5R00AI159380-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Caroline Guglielmetti
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $239,509
- **Award type:** 5
- **Project period:** 2023-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10933007

## Citation

> US National Institutes of Health, RePORTER application 10933007, Real time imaging of immune cells and glutamate dynamics by PET and metabolic MRI (5R00AI159380-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10933007. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*