# A Proof-of-concept of Vitamin B3 for Metabolic MR Imaging

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $251,490

## Abstract

Project Summary/Abstract
 This proposal aims for proof-of-concept of vitamin B3 as an MRI probe to image NAD (i.e.
Nicotinamide adenine dinucleotide) and its metabolic transformations in vivo. NAD is one of the
most important coenzymes in the cell. NAD plays vital roles in energy metabolism.. NAD is also a
key signaling molecule in cell homeostasis, lifespan regulation, DNA repair and telomere
maintenance. Recently, there has been a considerable interest in NAD as new studies have revealed
age-associated systemic NAD decline. In addition, studies have linked NAD biosynthesis to
pathophysiological mechanisms in several diseases, such as diabetes, non-alcoholic fatty liver
disease, retinal degeneration, multiple sclerosis, Alzheimer’s disease, or cancer. However, current
ability to image NAD metabolism in vivo is severely lacking. It is either limited by penetration depth
(i.e. optical imaging) or relies on radioactive tracer uptakes without providing direct information
about metabolic transformations (i.e. PET/SPECT). MRI suffers from limited signal to noise ratio.
 In mammals, NAD is synthesized from vitamin B3 precursors. We have dreamed of labeling
vitamin B3 with MRI-visible stable isotopes, enhancing the isotope signals by a million-fold by
hyperpolarization techniques, injecting, and imaging the metabolic conversions of hyperpolarized
vitamin B3 to NAD in vivo on an MRI scanner. Recent advances in hyperpolarized metabolic MR
imaging, pioneered by the PI and others, allow tracking metabolic conversions of hyperpolarized
13C-pyruvate to downstream metabolic products, resulting in new imaging biomarkers that inform
disease progression and guide treatment decisions. Similar techniques may be used to develop
hyperpolarized vitamin B3 for NAD imaging but to the best of our knowledge, this novel concept
has never been realized because it is unclear whether vitamin B3 has the right properties.
 The goal of this proof-of-concept proposal is to investigate the biochemistry and MR properties
of stable isotope-labeled vitamin B3 in ex vivo organs by using Mass Spectrometry (MS) and non-
hyperpolarized MR spectroscopy. We will obtain important information from the ex vivo data to
help us assess the likelihood of observing NAD as a downstream metabolic product of the injected
vitamin B3 within a few minutes of the hyperpolarization lifetime and estimate the signal to noise
ratio of NAD in important organs if labeled vitamin B3 was to be hyperpolarized and injected. The
proposed research will be guided by our extensive experience in radiotracer synthesis, MS analysis,
MR spectroscopy, and the development of new hyperpolarized probes. The success of the proposed
study will mark a critical milestone for the future development of vitamin B3 as a hyperpolarized
probe for metabolic imaging of NAD.

## Key facts

- **NIH application ID:** 9958092
- **Project number:** 1R21GM137227-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** YI-FEN YEN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $251,490
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9958092

## Citation

> US National Institutes of Health, RePORTER application 9958092, A Proof-of-concept of Vitamin B3 for Metabolic MR Imaging (1R21GM137227-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9958092. Licensed CC0.

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