# Imaging Biomarkers for Glioma Treatment Response

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $275,857

## Abstract

ABSTRACT
 Alteration of metabolism so as to favor a preponderance of glycolysis (GLY) relative to oxidative
phosphorylation (OXPHOS) is considered a hallmark of cancer. Known originally as the Warburg effect, and
now considered part of the larger concept of metabolic reprogramming, these cellular changes represent a way
for cancer tissue to support rapid proliferation by preserving carbon skeletons for biomass production.
Understanding the mechanisms that underlie this metabolic shift is an active area of research. In the context
of therapeutics, insights from recent studies provide strong support that this reprogramming phenotype is
necessary and sufficient to support the cancer process, thus providing a basis for highly novel therapeutic
strategies in which either blocking or reversing metabolic reprogramming is the goal. Furthermore, malignant
gliomas, highly glycolytic cancers exceedingly resistant to conventional treatments, seem particularly suited to
approaches that can subvert this phenotype, and we believe the most crucial obstacle to moving such
therapies to clinic has been the inability to reliably measure in vivo response to such metabolic therapies.
 The scientific premise of this proposal is that hyperpolarized 13C (HP13C) magnetic resonance imaging
(MRI) offers great promise in fulfilling this clinical need. Pyruvate (Pyr), located at a crucial juncture in the brain
glucose metabolic pathway where it can be either reduced to lactate (Lac) or converted to acetyl CoA + CO2,
which is then converted to bicarbonate (Bic), has the potential to be used as a HP13C surrogate marker of the
balance between GLY and OXPHOS. Following the bolus injection of HP [1-13C]Pyr, we propose that the
observed 13C-Lac/13C-Bic (Lac/Bic) ratios can be used as a quantitative biomarker of a changing balance
between these two metabolic processes, thus providing key information on glucose’s metabolic fate
complementary to the uptake information provided by more commonly available 18F-fluoro-deoxy-glucose
positron emission tomography (FDG-PET). Here, we propose to add simultaneous FDG-PET/HP13C/MRI
measurements to an upcoming Phase II clinical trial of malignant glioma treated with BPM31510 (Berg LLC), a
nano-suspension of Coenzyme Q10 showing high accumulation in cancer cell mitochondria and having marked
antitumor activity in multiple in vivo models (both alone and in combination with chemotherapeutic agents) with
in vitro evidence strongly suggesting the effect is mediated via increasing OXPHOS (i.e., reversing the
Warburg effect).
 Our overall goal is to assess the potential synergy of combining information on glucose uptake, as provided
by FDG-PET, and glucose metabolism, as provided by HP13C, for tumor characterization, assessment of
therapeutic response, and prediction of patient outcome. If successful, the results from this pilot study would
provide the critical preliminary data to justify larger follow-up studies of the use of these imaging biomarkers
w...

## Key facts

- **NIH application ID:** 10025488
- **Project number:** 1R01CA245097-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Lawrence D Recht
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $275,857
- **Award type:** 1
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025488

## Citation

> US National Institutes of Health, RePORTER application 10025488, Imaging Biomarkers for Glioma Treatment Response (1R01CA245097-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10025488. Licensed CC0.

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