# Metabolic imaging of hyperpolarized 13C pyruvate in polycystic kidney disease

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $117,711

## Abstract

In response to NIDDK’s NOSI NOT-DK-20-034 “Advancing Polycystic Kidney Disease (PKD) Research
through Catalytic Tool and Technology Development”, the overarching goal of this proposal is to develop new
metabolic imaging tools for investigating the metabolic alterations in PKD. Autosomal dominant PKD (ADPKD)
is the most common inherited renal disease and is estimated to affect 1/2500 to 1/1000 individuals worldwide.
However, there is currently no cure and additional therapies that will completely delay or prevent renal cyst
formation are still an unmet clinical need. Recently there has been increased interest in aspects of altered
metabolism in cystic cells with multiple lines of evidence suggesting that metabolic reprogramming is an
intrinsic component of the disease. Better understanding the relation between metabolic dysregulation and
cystogenesis could aid in identifying new therapeutic targets. One important discovery was the fact that the
deletion of a ADPKD gene, PKD1, upregulates the rate of glycolysis in a manner similar to the Warburg effect
in tumor cells. However, a current limitation of the methods investigating metabolic processes in ADPKD is that
they do not measure cellular metabolism in the normal microenvironment as they rely on in vitro assays. The
recent development of hyperpolarized (HP) 13C MR spectroscopy (MRS) enables for the first time the real-time
noninvasive measurement of critical dynamic metabolic processes in vivo. So far, the most widely used
substrate is [1-13C]pyruvate (Pyr) and it has been shown in both preclinical and clinical studies that its
conversion to lactate (Lac) is sensitive to the high glycolytic rates in tumors. Therefore, we propose first to
develop a HP 13C MRS-based approach for noninvasively assessing the metabolic reprogramming in ADPKD.
Specifically, we will develop optimized MR acquisition and quantification techniques for improved
metabolic imaging of both HP [1-13C] and [2-13C]Pyr and their respective metabolic products enabling
the simultaneous measurement of both glycolytic and mitochondrial metabolism (Aim 1). Secondly, we will
evaluate these techniques in their ability to detect altered kidney metabolism in a longitudinal study in
a murine model of ADPKD (Aim 2). If successful, metabolic imaging of HP Pyr would represent a critical
advance for both preclinical and clinical research of ADPKD and could add to the toolbox of personalized
medicine for patient care.

## Key facts

- **NIH application ID:** 10527162
- **Project number:** 1R21DK131357-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Dirk Mayer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $117,711
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527162

## Citation

> US National Institutes of Health, RePORTER application 10527162, Metabolic imaging of hyperpolarized 13C pyruvate in polycystic kidney disease (1R21DK131357-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10527162. Licensed CC0.

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