# Epigenetic Mechanisms in Alcohol Use Disorder quantified by non-invasive PET imaging

> **NIH NIH R33** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $592,193

## Abstract

Summary/Abstract
There is growing evidence suggesting that the epigenetic processes such as histone acetylation may play a
role in the alcohol-induced gene regulations and behavior. To date, the studies in animals demonstrated that
histone deacetylases (HDACs), at least HDAC2 and HDAC3, could induce histone-related epigenetic changes
after the treatment of ethanol. In addition, several studies have shown that HDAC inhibitors could be used to
counter ethanol-induced behaviors and the ethanol-induced changes of HDAC levels.
We have recently achieved a major research goal by developing a PET imaging agent, [11C]Martinostat that
selectively binds to a subset of HDAC enzymes. [11C]Martinostat has been full characterized as a novel and
the first PET radiotracer for epigenetic research through rodent imaging, non-human primates (NHPs) imaging
and pilot healthy human imaging. We are extremely excited to take a large step forward in understanding
epigenetic role in alcoholism by visualizing HDACs in the healthy and dysfunctional human brain in alcohol use
disorder (AUD) patients.
Together with the our multidisciplinary teams and strong collaborations, we are seeking the support through
the R21/R33 mechanism for this high-risk, high-reward study to characterize the density and distribution of key
HDACs throughout the brain of healthy subjects and in patients with alcoholism by applying our new PET
imaging probe.
Our initial data on [11C]Martinostat in humans strongly supports the success of our proposal for clinical imaging
in healthy subjects (Aim 1) and in AUD patients (Aim 2 and Aim 3) in R21/R33 phases. PET-MR imaging in
humans with [11C]Martinostat will deliver answers to fundamental questions about chromatin modifying
enzymes in the living human brain in a way that has not been possible until now and facilitate proof of
mechanism/target engagement in novel therapeutic trials.

## Key facts

- **NIH application ID:** 9975088
- **Project number:** 5R33AA025192-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Changning Wang
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $592,193
- **Award type:** 5
- **Project period:** 2016-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975088

## Citation

> US National Institutes of Health, RePORTER application 9975088, Epigenetic Mechanisms in Alcohol Use Disorder quantified by non-invasive PET imaging (5R33AA025192-05). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9975088. Licensed CC0.

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