# Updating Bifunctional Chelators to Keep Pace with Modern Biomedical Sciences

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $132,164

## Abstract

PROJECT SUMMARY
Exogenous metal chelates play an important role not only in the biomedical sciences but also in clinical
medicine. Metal chelates may be used for a variety of purposes that span both the diagnosis and treatment of
disease. One way in which the utility of metal chelates can be expanded is by tagging molecules of biological
interest. The biomolecule might be a protein, a fragment thereof, or any other relevant molecule, that has been
discovered to play a particular role in disease progression. The technology for conjugating metal chelates to
biomolecules is now well developed. An example of the application of this technology would be to tag a
relevant biomolecule with a metal chelate that can be detected using a common imaging modality. In
preclinical studies this allows us to learn more about disease, its progression and treatment. Translation to the
clinic may facilitate personal treatment regimens to be prescribed, rather than a one size fits all approach.
The down side to this approach, and the factor likely to limit clinical translation, is the inherent toxicity of metals
should they be liberated from the chelate in which they were administered. Exogenous metal chelates are
routinely used in clinical medicine and, providing that the excreted rapidly, they are safe. However, when
these chelates are retained in the body for prolonged periods, adverse effects can arise. To prevent release of
the metal it is necessary to ensure that the chelate is excreted much more quickly than the metal is able to
escape from the chelate. The longer the chelate remains in the body the more likely the metal ion is to be
released. The large biomolecules if interest for tagging with metal chelates either do not excrete at all, or do so
very slowly. And this increases the likelihood that toxicity problems will arise resulting from release of the
metal from the chelate. The inability to rapidly excrete the metal chelate tag limited the extent to which this
approach can be applied to nonhuman primate studies and ultimately translated into the clinic.
We will develop an adaptation to existing technology for tagging biomolecules with metals that is aimed at
overcoming these limitations. The specific aim of this project is to insert a linker between biomolecule and
metal chelate that will jettison the metal chelate after it has served its purpose. The small metal chelate thus
released can then be quickly and safely excreted. This new linker would afford a method by which the metal
chelate can both tag a relevant biomolecule and still be excreted in a timely manner. We anticipate that this
adaptation will expand the utility of metal chelate tags to a broader range of biomedical applications and
increase the scope for clinical translation.

## Key facts

- **NIH application ID:** 9995535
- **Project number:** 5R21GM127964-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** MARK WOODS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $132,164
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995535

## Citation

> US National Institutes of Health, RePORTER application 9995535, Updating Bifunctional Chelators to Keep Pace with Modern Biomedical Sciences (5R21GM127964-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9995535. Licensed CC0.

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