# Intratumoral imaging of hypoxia using 1H- and 19F-MRI with redox-responsive Eu-based contrast agents

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2021 · $656,139

## Abstract

There is a great need for positive contrast agents for magnetic resonance imaging (MRI) that respond to levels
of hypoxia in heterogeneous environments like those found in many tumors for the purpose of predicting
therapeutic outcomes, developing new therapies, and enabling the testing of hypotheses relevant to our
collective fundamental understanding between hypoxia and human health. Our long-term goal is to develop
positive contrast agents for MRI to fill this void in diagnostic medicine by focusing on EuII-containing complexes
that are among the most promising areas of study. The overall objective of this application is to establish the
groundwork necessary for translation of our new 19F-EuII-based complexes into useful hypoxia-responsive
contrast agents by studying the influence of the position of fluorine on ligands for europium and characterizing
in vitro and in vivo indices of hypoxia. The rationale that underpins the proposed research is that EuII-
containing complexes labeled with fluorine differentially (T1 or 19F) influence MRI as a function of the oxidation
state of europium as we have recently demonstrated both in vitro and in vivo. The expected outcome of this
proposal is the establishment of 19F-EuII-based contrast agents with defined hypoxia indices. This outcome is
expected to have a positive impact by contributing to the NIH's mission in the understanding of human
diseases. We plan to achieve the objective of the proposal by pursuing three specific aims: (1) to synthesize a
series of redox-active Eu-based multimodal contrast agents designed rationally from our initial successful
agent; (2) to characterize temperature-dependence of relaxivity and in vitro hypoxia indices for multimodal
redox-active 19F-Eu-based probes for MRI; and (3) To define in vivo hypoxia indices in healthy mice, hypoxic
mice, and mouse models of osteosarcoma. The new 19F-EuII-based probes will be significant because they are
expected to enable changes in hypoxia resulting from therapies to be imaged, consequently aiding in
assessing therapeutic efficacy and influencing the care and management of cancer patients. Furthermore,
because hypoxia is relevant to a wide-range of diseases, this proposal is expected to maximize returns in
many other investments of the NIH.

## Key facts

- **NIH application ID:** 10239104
- **Project number:** 5R01EB026453-04
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** MATTHEW J ALLEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $656,139
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239104

## Citation

> US National Institutes of Health, RePORTER application 10239104, Intratumoral imaging of hypoxia using 1H- and 19F-MRI with redox-responsive Eu-based contrast agents (5R01EB026453-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10239104. Licensed CC0.

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