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Measuring NAD+/NADH ratio in vivo using hyperpolarized 15N MRS

Award Number: R21EB038569
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Measuring NAD+/NADH ratio in vivo using hyperpolarized 15N MRS - Abstract The NAD+/NADH redox system enables hydride transfer and subsequent ATP generation through mitochondrial oxidative phosphorylation. NADH accumulates when cells are deprived of oxygen (hypoxia or ischemia) or when the electron transport chain is impaired. Therefore, decreased NAD+/NADH ratio is observed in a variety of diseases involving mitochondrial dysfunction such as diabetes, cancer and ischemic attack. Decreasing NAD+/NADH ratio decreases with age promoting cellular senescence via decreasing sirtuin activity. NAD+- precursors that boost in vivo NAD+ levels, most prominently, nicotinamide riboside, are now widely sold as supplements to counteract the detrimental effects of aging and to extend life-span. The diagnostic value of the NAD+/NADH ratio has been long recognized. Yet, currently there is no analytical or spectroscopic technique that could be used to assess NAD+ metabolism and the NAD+/NAD ratio in vivo in a non-invasively in a spatially resolved manner across various tissues. In this project we propose to develop hyperpolarized 15N-labeled nicotinamide riboside (NR) as a 15N magnetic resonance spectroscopy (MRS) probe to monitor NAD+ and NADH levels in vivo. NR is taken up and rapidly converted to NAD+ and in virtually all tissues. 15N MRS can detect and quantify NAD+ and its reduced form, NADH, independently from each other allowing the real-time monitoring the NAD+/NADH ratio. An NMR signal enhancement (hyperpolarization, or HP) technique, namely, dissolution dynamic nuclear polarization, and 15N enrichment will be used to improve the sensitivity of detection. The goals of the project will be achieved in two Specific Aims. Aim 1 will focus on the synthesis and hyperpolarization of 15N-labeled nicotinamide riboside. In Aim 2, HP-15N MRS studies will be performed in cells and in vivo in renal ischemia rat model to show that HP-[15N]nicotinamide riboside can be used to assess the NAD+/NADH ratio in normal and ischemic tissues. If successful, the proposed approach would have significant applications in both clinical practice and basic research.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $207,500 )
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	8/18/2026	NEW	$207,500
														Subtotal = $207,500

Grand Total All Awards = $207,500

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Measuring NAD+/NADH ratio in vivo using hyperpolarized 15N MRS

Award Number: R21EB038569

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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