# TR&D 1: The Chemistry of New Imaging Agents

> **NIH NIH P41** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $298,359

## Abstract

Project Summary/Abstract 
Metabolic imaging using hyperpolarized (HP) 13C and 15N substrates offers the potential to monitor 
intermediary metabolism in tissues throughout the human body. HP-[1-13C]pyruvate is the molecule most 
widely used in HP studies, but there are several other TCA cycle intermediates that meet the requirements 
of a good metabolic imaging candidate probe. In this TR&D Project we propose to develop new 13C- and 
15N-enriched compounds as reporters of tissue physiology and metabolism. We will apply these 
hyperpolarized sensors to measure important physiological parameters at sensitivity levels never before 
achieved by MRI. One of the main thrusts of this proposal is to develop HP-13C labeled mono-esters of 
TCA cycle intermediates to image whole-body glucose production because this could potentially have an 
enormous impact on development of new drugs to control glucose levels in type 2 diabetic patient 
populations. Thus, Aim 1 will focus on the design, synthesis and DNP hyperpolarization of monoesters of 
13C-labeled TCA cycle intermediates such as [4-13C]oxaloacetate-1-ethyl ester, [4-13C]malate-1-ethyl ester, 
and [1-13C]-2-ketoglutarate-4-ethyl ester. The 13C-enriched carbon in these molecules should display long 
T1 values and these derivatives should enter hepatocytes quickly via mono-carboxylate transporters and 
hydrolyze to their respective dicarboxylate intermediates. 15N is another attractive nucleus for the design of 
HP-probes but its potential for metabolic imaging has largely remained unexplored. In Aim 2 novel 15N- 
labeled molecular design platforms are proposed that will yield HP-15N-agents for imaging pH and free 
Zn2+-levels in zinc-rich tissues.. Considering the fact that HP-[1-13C]pyruvate is the most popular molecule 
of choice for metabolic MR imaging, in Aim 3, a practical chemical approach will be developed to produce 
gram quantities of HP-[1-13C]pyruvate by starting with an ester of pyruvate and para-H2. If we are 
successful, this would make HP-[1-13C]pyruvate more widely available to MRI clinics across the country for 
molecular imaging of cancer and other metabolic diseases. The overarching goal of this core project is to 
develop and implement novel hyperpolarized agents in vivo to image important biomarkers and metabolic 
pathways in type 2 diabetes, cancer and other diseases.

## Key facts

- **NIH application ID:** 10135977
- **Project number:** 5P41EB015908-33
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Dean Sherry
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $298,359
- **Award type:** 5
- **Project period:** 1997-09-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135977

## Citation

> US National Institutes of Health, RePORTER application 10135977, TR&D 1: The Chemistry of New Imaging Agents (5P41EB015908-33). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135977. Licensed CC0.

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