# Library Synthesis and Screening of Eu(II)-Based Contrast Agents

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2021 · $315,613

## Abstract

There is a great need for contrast agents for magnetic resonance imaging (MRI) that respond to changes in
redox environment to enable the facile monitoring of responses to new therapies, to guide cancer treatment
selection, to image early responses for driving treatment development, and to enable the testing of hypotheses
relevant to the collective fundamental understanding between redox environment and human health. The long-
term goal of the research project 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 new Eu-based
complexes into useful redox-responsive contrast agents by assembling and screening a library of EuII- and
EuIII-containing complexes for their thermodynamic stability, kinetic inertness, and relaxivity. The rationale that
underpins the proposed research is that EuII can be stabilized against oxidation and rendered non-toxic in vivo
through ligand modification, as recently demonstrated; that the ideal ligand system will coordinate both EuII and
EuIII; and that ligands that bind both oxidation states can be rationally designed with the information gained by
studying a library of complexes. The expected outcome of this proposal is a great strengthening of the
chemical foundation for the development of redox-responsive, Eu-based complexes for use as contrast agents
in MRI. This outcome is expected to have a positive impact by contributing to the NIH's mission in the
diagnosis of human diseases and development of new therapies. The objective of the proposal is expected to
be achieved by pursuing three specific aims: (1) to assemble a library of ligands composed of synthesized
cryptands and commercially available noncryptand ligands; (2) to screen ligands with EuII and with GdIII for T1-
shortening indicative of complex formation; and (3) to characterize the thermodynamic stability, kinetic
inertness, and relaxivity of EuII- and EuIII-containing complexes. The new Eu-based probes will be significant
because they are expected to enable changes in redox environments resulting from therapies to be imaged,
consequently, aiding in treatment development and selection and increasing the basic understanding of the
relationship between redox homeostasis and human health. Furthermore, because redox homeostasis 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:** 10093042
- **Project number:** 5R01EB027103-03
- **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:** $315,613
- **Award type:** 5
- **Project period:** 2019-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10093042

## Citation

> US National Institutes of Health, RePORTER application 10093042, Library Synthesis and Screening of Eu(II)-Based Contrast Agents (5R01EB027103-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10093042. Licensed CC0.

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