# Para-hydrogen induced polarization of 13C labeled TCA cycle metabolite precursors

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $246,000

## Abstract

Abstract
In vivo 13C MRS/MRI offers the unique opportunity to observe various metabolic processes in real time as they
happen when enabled by a hyperpolarization technique. The most common technique for hyperpolarization is
dissolution Dynamic Nuclear Polarization (DNP). DNP works by enhancing the NMR signal via the microwave-
driven polarization transfer from electrons to target nuclei. While dissolution DNP-NMR can produce dramatically
enhanced liquid state NMR signals, it has severe limitations including expensive hardware, the need for a free
radical polarizing agent, extended polarization build-up time at cryogenic temperatures and batch-wise operation.
An alternative technique for 13C hyperpolarization is para-hydrogen induced polarization (PHIP), which involves
the chemical addition of para-hydrogen (hydrogen gas enriched in the para spin isomer) to unsaturated
substrates followed by the conversion of the singlet spin order of the para-H2 into 13C spin polarization by
magnetic field cycling. Although PHIP requires specific chemistry, the advantages of PHIP over DNP make this
technique very appealing: it is far less expensive, faster and capable of the large-scale production of
hyperpolarized samples, potentially in a continuous flow manner. In this exploratory project we will develop
innovative chemistries (13C-enriched, unsaturated precursors to important metabolites and novel catalyst
systems) that will significantly widen the scope of PHIP for 13C metabolic studies. The goal of Aim 1 is the
synthesis and PHIP of 13C-labeled, unsaturated precursors to 2-ketoglutarate, an important intermediate of the
TCA cycle. In Aim 2, we will explore the PHIP of O-acetylated enol derivatives of 13C labeled pyruvate and
oxaloacetate. Catalytic hydrogenation of these intermediates will yield lactate and malate derivatives. A major
goal of this aim will be the development of chiral catalyst systems that would preferentially afford the natural L-
form of these important metabolites.

## Key facts

- **NIH application ID:** 10434648
- **Project number:** 5R21EB030765-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Zoltan Kovacs
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $246,000
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434648

## Citation

> US National Institutes of Health, RePORTER application 10434648, Para-hydrogen induced polarization of 13C labeled TCA cycle metabolite precursors (5R21EB030765-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10434648. Licensed CC0.

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