# Project 2: Novel hyperpolarized C-13 imaging as metabolic markers of response in IDH mutant glioma

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $409,607

## Abstract

Project Summary/Abstract
Isocitrate dehydrogenase (IDH) mutant glioma are mostly non-enhancing, which makes it difficult to distinguish
the boundaries of infiltrative lesions from normal tissue and edema in both newly diagnosed and post-treatment
settings. The standard efficacy endpoints of response rate or overall survival are also challenging for such slow
growing tumors. These limitations have led to the consideration of innovative imaging approaches to improve
the characterization of tumor burden and early assessment of treatment response. Expanding imaging
capabilities to include robust metrics to describe the biological properties of lesions could be important to assess
the population of IDH mutant glioma that are associated with specific metabolic reprogramming, slow growth
rate, and high risk of malignant transformation.
The proposed project will leverage our experience in the clinical implementation of hyperpolarized [1-
13C]pyruvate imaging for glioblastoma in the previous cycle to assess dynamic metabolism in IDH mutant glioma.
Metabolic reprogramming in IDHm tumors specifically results in the conversion of alpha-ketoglutarate (⍺-KG) to
a novel oncometabolite 2-hydroxyglutarate (2HG), with a concomitant decrease in conversion of ⍺-KG to
glutamate. Dynamic metabolic conversions in IDHm glioma can, therefore, be measured using novel imaging
probes HP [2-13C]pyruvate and [1-13C] (⍺-KG). We will first establish the preclinical utility of using [2-13C]pyruvate
and [1-13C] ⍺-KG as a non-invasive imaging biomarker of treatment response and tumor burden in Aim 1. In Aim
2, we will take advantage of ongoing clinical trials at UCSF that specifically target the metabolism of IDH mutant
glioma to assess the impact of using dynamic hyperpolarized [2-13C]pyruvate imaging to assess early metabolic
changes in patients undergoing treatment. Aim 3 will improve the characterization of tumor burden in newly-
diagnosed and recurrent IDH mutant glioma patients using hyperpolarized [1-13C] ⍺-KG metabolic imaging with
correlation to tissue characteristics. Ultimately, we plan to translate dynamic, non-invasive metabolic imaging
biomarkers to enhance the evaluation of novel therapies and assist in the optimal management of IDHm patients.

## Key facts

- **NIH application ID:** 10920406
- **Project number:** 5P50CA097257-22
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Susan M Chang
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $409,607
- **Award type:** 5
- **Project period:** 2002-09-20 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10920406

## Citation

> US National Institutes of Health, RePORTER application 10920406, Project 2: Novel hyperpolarized C-13 imaging as metabolic markers of response in IDH mutant glioma (5P50CA097257-22). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10920406. Licensed CC0.

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