# Outer sphere tuning of a Eu(II)-containing contrast agent for imaging hypoxia via MRI

> **NIH NIH F30** · WAYNE STATE UNIVERSITY · 2024 · $44,619

## Abstract

Project Abstract
The ability to image oxygen in vivo has important diagnostic, prognostic, and therapeutic implications because
hypoxia is correlated with aggressive disease states and resistance to many types of treatments. EuII/III-based
systems for magnetic resonance imaging (MRI) are an attractive approach for imaging hypoxia due to their
potent oxygen-sensing capabilities. EuII produces bright T1-weighted images, but oxidation of EuII by O2 produces
EuIII that does not positively enhance images. Our lab has demonstrated that EuII-containing contrast agents can
be used for imaging hypoxia in tumors in vivo and that EuII/III-based contrast agents are compatible with multiple
imaging modalities including 1H- and 19F-MRI, chemical exchange saturation transfer, and photoacoustic
imaging. Although these results are promising, the short half-life of EuII in vivo is the critical barrier to imaging
hypoxia in a wide range of environments using the EuII/III redox couple because the rapid oxidation of EuII at
physiologically normal levels of pO2 limits the administration of the EuII-containing contrast agents to injection
directly at sites of interest and prevents ratiometric imaging using multiple modalities. Our overarching goal is
to increase persistence of EuII long enough to enable systemic delivery and ratiometric imaging of hypoxic
regions in a wide range of diseases. We propose to address the critical limitation of the persistence time of
EuII in oxygenated environments by modulating factors that kinetically hinder oxygen approach in the
outersphere. We previously showed that a perfluorocarbon-soluble EuII-containing complex, EuII1, dispersed in
a perfluorocarbon nanoemulsion has increased persistence times in vitro and in vivo as seen by 19F MRI. Our
working hypothesis is that altering factors of gas diffusion will afford control over persistence of EuII1 in
oxygenated environments. Aim 1 studies the solubility of O2 in nanoemulsions consisting of different
perfluorocarbons with varying abilities to dissolve O2. Aim 2 investigates the influence of Henry’s and Graham’s
laws of gas diffusion on the persistence of EuII using different gasses to perfuse into perfluorocarbon
nanoemulsion to act as a counter pressure against O2 diffusion. In Aim 3, the effect of the size of nanoparticles
in the perfluorocarbon nanoemulsion is studied with respect to the persistence of EuII. The expected outcomes
of this proposal are (1) a better understanding of factors that influence the kinetic outersphere approach of O2
to EuII dispersed inside perfluorocarbon nanoemulsions and (2) persistence times of EuII1 in vivo that are long
enough to enable systemic injection and ratiometric imaging.

## Key facts

- **NIH application ID:** 10995737
- **Project number:** 1F30EB035471-01A1
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Andrea Batchev
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $44,619
- **Award type:** 1
- **Project period:** 2025-02-01 → 2030-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995737

## Citation

> US National Institutes of Health, RePORTER application 10995737, Outer sphere tuning of a Eu(II)-containing contrast agent for imaging hypoxia via MRI (1F30EB035471-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10995737. Licensed CC0.

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