# PET Tracers for Imaging ROS Activity

> **NIH NIH P41** · WASHINGTON UNIVERSITY · 2024 · $259,577

## Abstract

TR&D 3 Project Summary
Reactive oxygen species (ROS) regulate critical physiological functions. However, the imbalance in
production/mitigation of ROS also mediates pathogenesis of numerous diseases ranging from cardiovascular
sciences to oncology clinic. Through the current funding cycle of TR&D3 program, we have identified a lead PET
tracer (described herein as {68Ga}Galuminox) for imaging systemic inflammation and demonstrate its ability to
monitor LPS-induced inflammation within lungs (acute lung injury model), monitor β3 integrin-mediated
chemoresistance in breast cancer bone metastases, and kidney injury in nephrotic syndrome model. Importantly,
Galuminox provides a sensitive readout of mitochondrial ROS (mROS) in human cells. Combined data indicate
make {68Ga}Galuminox a worthy candidate of its advancement for regulatory approvals to evaluate safety
through human dosimetry studies. Given its desirable trait to serve as a redox sensitive reporter probe,
Galuminox also provides a template scaffold for generation and validation of copper-64 or fluorine-18
counterparts (with shorter positron range) as alternative PET tracers. Unfortunately, Galuminox analogues would
not penetrate blood brain barrier (BBB) thus limiting their utility for assessing ROS mediated systemic
inflammation. To achieve functional imaging of mROS within the brain, we have rationally designed small
heterocyclic molecule ({18F}SLN128). Like Galuminox, SLN-128 is a highly fluorescent probe thus allowing
opportunities for dual optical-PET readout for its biochemical validations. Compared with Galuminox which
detects superoxide and hydrogen peroxide, SLN128 detects superoxide and hydroxyl radical. Given that both
radiotracers have two different PET radionuclides and offer different detection capabilities, we anticipate that
both PET molecular imaging probes could provide complementary information of oxidative imbalance mediating
pathogenesis of both non-CNS and CNS diseases. Specific aims of TRD3 renewal are: Aim 1: Evaluate safety
of {68Ga}Galuminox through human dosimetry studies following regulatory approvals. Aim 1.1: Evaluate the
performance of {68Ga}Galuminox for imaging inflammation using rodent models of ischemic- and bacterial
exotoxin-induced acute lung injury as well as other models of oxidative stress acute respiratory distress
syndrome (ADRS), cystathionine γ-lyase (CSE) -mediated ischemic vascular remodeling, and meningeal ROS
in MS through the Collaborative Projects. Aim1.2: To compensate for higher positron range of gallium-68 in
Galuminox and allow options for delayed imaging in gastrointestinal tract, we propose to synthesize,
biochemically characterize Cu-64 and F-18 counterparts of Galuminox and evaluate their pharmacokinetic
profiles in diseased rodent models. Aim 1.3: As an exploratory aim, we also propose to design and develop
small organic heterocyclic molecules for assessment of mROS prevalent in pathogenesis of neurodegenerative
diseases. These produ...

## Key facts

- **NIH application ID:** 10914211
- **Project number:** 5P41EB025815-07
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Vijay Sharma
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $259,577
- **Award type:** 5
- **Project period:** 2018-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914211

## Citation

> US National Institutes of Health, RePORTER application 10914211, PET Tracers for Imaging ROS Activity (5P41EB025815-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10914211. Licensed CC0.

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