# Diagnosis of low-grade glial tumors using 11C glutamine isotopomers

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $242,250

## Abstract

This proposal focuses on the development and validation of glutamine-derived 11C isotopomers for positron
emission tomography. Specifically, the 1- and 5-positions of exogenously administered glutamine have
different metabolic fates, depending on the dominant mechanisms of conversion present. We will therefore
synthesize both L-[1-11C]glutamine ([1-11C]gln) and L-[5-11C]glutamine ([5-11C]gln), and investigate their use in
detecting the isocitrate dehydrogenase mutation (IDHm), seen in several benign and malignant clinical
diseases including low-grade glioma (LGG). Improved diagnosis of LGG would address a major challenge that
neuro-radiologists, neuro-oncologists, radiation oncologists and neuro-surgeons encounter frequently, namely
differentiating glial tumor from other brain entities. Patients with IDH-mutant (IDHm) glioma harbor the
oncometabolite 2-hydroxyglutarate (2HG), which represents a promising way to detect LGG. We are motivated
by a recent report establishing rapid conversion of exogenous glutamine to 2HG in IDHm lesions, representing
a way to sequester the 11C radionuclide. The central hypothesis of this proposal is that a positron-
labelled metabolic precursor of 2HG, [1-11C]gln, can be used to detect IDHm. We further predict
significant advantages in using [1-11C]gln versus the reported [5-11C]gln isotopomer, based on the suppression
of background signals related to tricarboxylic acid (TCA) cycle metabolism. When validated, this approach
would set the stage for clinical use of [1-11C]gln PET in evaluating LGG and other IDHm lesions.
We propose a multi-PI and interdisciplinary collaboration to validate [1-11C]gln PET as an IDHm-specific tool
and perform the first patient studies using [1-11C]gln to further support the methodology. We will first develop
the first radiosynthesis of [1-11C]gln, via adaptation of reported methods using [11C]CO2 and [11C]CN-. We will
then compare the accumulation of [1-11C]gln to that of [5-11C]gln in IDHm versus IDH-wildtype (IDHwt) cells,
both in vitro and in vivo (Specific Aim 1). In Specific Aim 2, all regulatory work and site approvals needed to
study [1-11C]gln at UCSF will be accomplished. In Specific Aim 3, we will translate [1-11C]gln under the
Radioactive Drug Research Committee (RDRC) program and study its performance in patients suffering from
LGG. While this application focuses on LGG, a clinically translatable IDHm-specific tracer would revolutionize
the workup and management of a large variety of clinically relevant lesions. Furthermore, robust methods to
synthesize and evaluate amino-acid derived 11C isotopomers will dramatically improve the ability of PET to
detect metabolic reprogramming in human disease.

## Key facts

- **NIH application ID:** 10458049
- **Project number:** 5R21EB030899-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Javier Villanueva-Meyer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $242,250
- **Award type:** 5
- **Project period:** 2021-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458049

## Citation

> US National Institutes of Health, RePORTER application 10458049, Diagnosis of low-grade glial tumors using 11C glutamine isotopomers (5R21EB030899-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10458049. Licensed CC0.

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