# Validation of imaging brain tumor metabolism using deuterated glucose

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $494,260

## Abstract

Aberrant metabolism is increasingly recognized as a hallmark of cancer. The Warburg effect is a well-known
example of such abnormal cancer metabolism, which entails a shift away from oxidative to glycolytic glucose
metabolism (despite the presence of oxygen) and usually also increased glucose uptake. The detection of this
increased glucose uptake, via a radioactive analogue (2-18F-fluoro-2-deoxy-D-glucose, FDG) with positron
emission tomography (PET), is often used for diagnosis, staging, and evaluating disease progression of tumors
outside the brain. However, in patients with brain tumors FDG-PET is frequently inconclusive because the normal
high glucose uptake in healthy brain is comparable to that in tumors, thereby obscuring the tumor-to-brain image
contrast. As a result, FDG-PET is not frequently used in these patients. That leaves brain tumor patients without
the benefits of metabolic imaging, which has a significant negative impact on the management of their disease.
 The recently developed MRI-based method, deuterium metabolic imaging (DMI) can be an alternative
strategy to detect abnormal glucose metabolism. DMI is based on 3D deuterium (2H) magnetic resonance
spectroscopic imaging (MRSI). After administration of the nonradioactive deuterated glucose, DMI can detect
both glucose and its downstream metabolites lactate and glutamate. In cancer cells that show the Warburg effect
the 2H-labeling in lactate and glutamate reflects the typical shift from oxidative to glycolytic metabolism. DMI can
detect this 2H-labeling and reveal the cancer-specific glucose metabolism with high tumor-to-brain image
contrast. Because of these features and the ease of use of the method, DMI can become a robust metabolic
imaging technique for brain tumors that so far has been missing.
 The goal of this proposal is to validate DMI of glucose metabolism as a potential imaging tool for
neurooncology, particularly for glioblastoma, the most common and lethal primary brain tumor. We envision that,
for patients with brain tumors, DMI can provide a similar benefit as FDG-PET has for many patients with tumors
outside of the brain. In Aim 1 we therefore seek to validate the 2H-labeling pattern in lactate and glutamate
detected with DMI as surrogates of the Warburg effect, by comparing them with absolute measurements of the
Warburg effect in rodent models of GBM. Aim 2 is focused on the potential of DMI to provide an early biomarker
of response to standard of care chemotherapy. To confirm the improved performance of DMI relative to current
clinically available methods, in Aim 3 metabolic maps generated by 1H MRSI, FDG-PET and DMI, are compared
for tumor-to-brain image contrast in patients with GBM. The proposed aims will provide better understanding of
the fundamental processes underlying the DMI-based image contrast, provide the first insight in its value for
monitoring therapy and disease progression, and benchmark its performance as a new metabolic imaging
method. Thes...

## Key facts

- **NIH application ID:** 10560260
- **Project number:** 1R01EB033764-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** ROBIN A DE GRAAF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $494,260
- **Award type:** 1
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10560260

## Citation

> US National Institutes of Health, RePORTER application 10560260, Validation of imaging brain tumor metabolism using deuterated glucose (1R01EB033764-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10560260. Licensed CC0.

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