# First-in-Human evaluation of an astrocytic glutamate transporter (EAAT2) PET tracer in healthy and Alzheimer's diseased brain

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $816,825

## Abstract

PROJECT SUMMARY
Alzheimer’s disease (AD) and related dementias represent a growing public health concern with tremendous
impact on patients and their families. Efforts to treat AD effectively are partially confounded by different
hypotheses regarding its initiation and progression. The varying hypotheses are reflected in the range of highly
informative imaging methods used to study AD and its progression, such as positron emission tomography
(PET) targeted to specific cerebral proteins. In this project we will develop a novel [18F]-labeled PET imaging
tracer, RP-115, to evaluate changes in astrocytes in healthy versus cognitively impaired AD patients by
quantitative PET imaging of the excitatory amino acid transporter 2 (EAAT2) that is primarily localized on
astrocytes and is significantly down-regulated in select cerebral regions of AD brain.
 The project hypothesis is that regional cerebral decreases of RP-115 tracer binding to astrocyte EAAT2
detected by PET imaging in live human brain can be used as an early and sensitive measure of AD onset and
progression. The first-in-human project objective is composed with two translational development goals: 1) to
establish RP-115 tracer human safety, and 2) to utilize the tracer to assess regional cerebral EAAT2 tracer
binding differences in healthy vs. Ab-, pTau- and cognitively-defined AD patients; and compare the EAAT2 AD
data to existing AD FDG and MAO-B astrocytic-related PET profiles. We will test the hypothesis and satisfy the
translational project objective by accomplishing three Specific Aims. Aim 1: Establish RP-115 safety in the
clinic with male and female PET imaging. Aim 2: Acquire RP-115 EAAT2 imaging data in well-defined male
and female healthy control and AD patient cohorts. Aim 3: Analyze the PET imaging data.

## Key facts

- **NIH application ID:** 10683344
- **Project number:** 5R01AG072743-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** JOHN M GERDES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $816,825
- **Award type:** 5
- **Project period:** 2022-08-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683344

## Citation

> US National Institutes of Health, RePORTER application 10683344, First-in-Human evaluation of an astrocytic glutamate transporter (EAAT2) PET tracer in healthy and Alzheimer's diseased brain (5R01AG072743-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10683344. Licensed CC0.

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