# Administrative Supplement to Existing NIH Grant-Purchase of a Equipment

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2024 · $14,241

## Abstract

Project Summary/Abstract
Malignant brain tumors are aggressive cancers that have high proliferative rates with much higher
energy requirements and high mortality rates. Despite intense clinical and drug development
efforts in the last two decades, there has been no improvement in survival. To support the
abnormal growth commonly seen in tumors, the cancer cells have altered their metabolism
compared to normal cells in healthy tissues. Most of the knowledge to date on cancer metabolism
is derived from cultured cell lines. Probing metabolism in intact tumors will be critical to understand
how the tumor cells grow in a patient under the complex biological tumor environment. From our
pilot study involving a small number of patients, we have demonstrated that gliomas and brain
metastases have the capacity to oxidize acetate in the citric acid cycle to meet their bioenergetic
requirements, and glucose and acetate together contribute up to 63.0% of the total acetyl-CoA
pool in these tumors. The remaining acetyl-CoA that provides carbon sources for biomolecular
synthesis, must be derived from other nutrients. The following are the goals of this proposal: (1)
determine if acetate and ketone body (beta hydroxybutyrate, BHB) utilization is a common
property of all gliomas or specifically linked to high grade GBMs (2) examine whether acetate and
BHB provide carbons for 2-hydroxyglutarate (2-HG) synthesis in IDH mutated glioma patients (3)
preclinical testing of the effects of small molecule inhibitors of acetate and BHB, in freshly resected
tumor tissue slices. We have Institutional Review Board (IRB) approved clinical protocol to infuse
non-toxic and non-radioactive 13C-enriched acetate in patients who will be undergoing surgical
removal of a brain tumor. Using Nuclear Magnetic Resonance (NMR) spectroscopy and mass
spectrometry of these surgically resected tumor tissues, we will investigate the above described
aims on energy metabolism of primary brain tumors. The attractiveness of this technology is that
no radioactivity is involved. We anticipate that the outcome of this study will generate a detailed
understanding of in vivo utilization of acetate and ketone body in brain tumor patients. This
knowledge will lead to identification of key metabolic targets that may be further exploited for the
development of new therapies. Additionally, it may identify novel biomarkers which may be helpful
in designing non-invasive in vivo MRI methods to track acetate utilization by tumors for diagnostic
purposes.

## Key facts

- **NIH application ID:** 11052058
- **Project number:** 3R01CA272763-01A1S1
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** Kumar Pichumani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $14,241
- **Award type:** 3
- **Project period:** 2024-04-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11052058

## Citation

> US National Institutes of Health, RePORTER application 11052058, Administrative Supplement to Existing NIH Grant-Purchase of a Equipment (3R01CA272763-01A1S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11052058. Licensed CC0.

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