# Imaging bacterial infection using deuterium-enriched sugar alcohols.

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $201,875

## Abstract

PROJECT SUMMARY:
This application addresses a major challenge that radiologists and other physicians encounter frequently,
namely distinguishing active infection from other processes in the human body. In response to this challenge,
our laboratory has developed both hyperpolarized 13C MRI and positron emission tomography (PET) tools
targeting bacteria-specific metabolism. In this proposal, we employ another nuclear magnetic resonance
(NMR)-observable stable isotope namely deuterium (2H) to detect living microorganisms both in vitro and in
vivo. In doing so we address two major challenges of 2H magnetic resonance imaging (MRI) by (1) identifying
2H MRI-observable metabolites that have the needed chemical shift separation from HDO (water) and (2) using
bacteria-specific sugar alcohols whose incorporation into microorganisms is not easily saturated. Our approach
also takes advantage of two different strategies to incorporate 2H in a microorganism-specific way, and newly
developed 2H MRI methods to maximize sensitivity.
The two detection strategies pursued are either (1) a 2H substrate is converted to a dominant, 2H-MRI
observable downstream metabolite or (2) a 2H substrate is converted to a dead-end metabolite that is
accumulated as a 2H-MRI detectable species. These two concepts are highlighted by enriched variants of
sorbitol, either D-[6,6'-2H2]sorbitol whose metabolism may be detected by its conversion to lactate/ethanol, or
2-deoxy-D-[2,2'-2H2]sorbitol anticipated to be “trapped” as its 6-phosphorylated adduct in bacteria. In both
cases, the 2H nuclei have the needed chemical shift for in vivo 2H MRI imaging. In addition, the technologies
pursued are amenable to clinical translation; our long-term goal is application of nontoxic 2H sugar alcohols to
vulnerable populations including children, without the need for ionizing radiation. We will first adapt an NMR-
compatible bioreactor for use in investigating 2H substrate metabolism in bacteria in vitro (Specific Aim 1).
We will show then show bacteria-specific incorporation of 2H using enriched substrates, that are either
metabolized to dominant 2H-MRI detectable products, or retained as dead-end molecules by pathogens
(Specific Aim 2). In Specific Aim 3, we will show that 2H MRI at 14T using these tools can detect living
bacteria in vivo.

## Key facts

- **NIH application ID:** 10430258
- **Project number:** 5R21AI164684-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** David M Wilson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2021-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10430258

## Citation

> US National Institutes of Health, RePORTER application 10430258, Imaging bacterial infection using deuterium-enriched sugar alcohols. (5R21AI164684-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10430258. Licensed CC0.

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