# TR&D 3: Imaging Carbohydrate Metabolism

> **NIH NIH P41** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $422,869

## Abstract

Project Summary/Abstract
Biochemical imaging using hyperpolarized (HP) nuclei now offers the possibility of extending the inherent
power of 13C NMR to rapidly image intermediary metabolism in human patients. The recent installation of a
clinical polarizer in this BTRC provides the opportunity to test and validate this technology as it moves towards
clinical research applications. The overall intent is to develop a good understanding of how to interpret 13C
NMR spectra and images from the liver after injection of HP-[1-13C]pyruvate and other substrates. A general
theme in this TR&D project is to perform conventional 2H and 13C isotopomer analysis and hyperpolarization
exams in the same tissue. With this approach, standard tracer methods are used to efficiently validate and
interpret the HP data. Aim 1 will focus on the utility of HP [1-13C]pyruvate for monitoring TCA cycle flux and
pathways related to gluconeogenesis in a rat model. Pharmacological and nutritional interventions will be used
to selectively manipulate specific aspects of liver metabolism. The sensitivity of HP data to these interventions
will be tested, and critically compared to results from simultaneous 2H and 13C NMR isotopomer analysis. In
Aim 2 we will investigate novel probes such as HP-[2-13C]dihydroxyacetone for imaging phosphoenol pyruvate
(PEP). 13C labeled mono-esters of TCA cycle intermediates, developed in TR&D 1, will also be evaluated in
vivo. With our collaborators, we have already determined that detection of HP-[1-13C]lactate, HP-[1-
13C]alanine and HP-[13C]bicarbonate from the liver is feasible in the pig. Consequently Aim 3 will test the
effects of nutritional state on gluconeogenic pathways and TCA cycle flux, using conventional methods, and at
the same time perform HP spectroscopy and imaging after injection of HP-[1-13C]pyruvate. Parallel
experiments in the same animals with an identical protocol will be performed with [U-13C]pyruvate, not
hyperpolarized, to measure the fraction of exogenous pyruvate entering the malate, lactate, alanine and acetyl-
CoA pools. These methods will be extended to human subjects in Aim 4 where we will monitor metabolism of
HP-[1-13C]pyruvate in the liver and evaluate the impact of simple alterations in nutritional state. The primary
goal is to implement hyperpolarization exams in the human liver and to critically evaluate the metabolic
information resulting from these exams.

## Key facts

- **NIH application ID:** 9850595
- **Project number:** 5P41EB015908-32
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Craig R Malloy
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $422,869
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850595

## Citation

> US National Institutes of Health, RePORTER application 9850595, TR&D 3: Imaging Carbohydrate Metabolism (5P41EB015908-32). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9850595. Licensed CC0.

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