# OTOENDOSCOPE PAIRED AGENT IMAGING OF OPIOID RECEPTOR KINETICS DURING DEPENDENCY AND WITHDRAWAL

> **NIH NIH R21** · DARTMOUTH-HITCHCOCK CLINIC · 2020 · $185,096

## Abstract

Summary / Abstract
Opioid abuse is now a full-fledged epidemic in the United States. The CDC estimates that over 165,000 people
have died from prescription opioid overdoses since 1999, and that 3,900 people start nonmedical use of
prescription opioids each day. As a result, opioid use disorder (OUD) costs society an estimated $55 billion per
year—twice the annual budget of the entire NIH. Most individuals with OUD began taking opioids on the advice
of their physician to manage pain from work injury or injury sustained during military service, often without any
knowledge of the risks of dependency. It is increasingly clear that the risks of dependency and addiction were
greatly underestimated by the scientific community as well, that the most commonly administered opioids have
among the highest physical and physiological dependence potentials of any abused class of drugs. However,
genetic differences within the naïve population predispose certain individuals to OUD once they are exposed to
opioids in a clinical setting or otherwise. These genetic differences result in mu-opioid receptor (MOR)
phenotypes that differ in binding, desensitization and internalization behavior—differences which are associated
with higher risk of addiction and higher severity in withdrawal symptoms (the biggest predictor of relapse). Paired
agent imaging (PAI) is an established method that can quantify receptor-ligand binding potential (BP) in vivo,
and could the ability to measure rate of receptor internalization if fluorescent agonist and antagonist pairs are
used instead of untargeted/targeted agent pairs. These two parameters—internalization rate and binding
potential—are hypothesized to predict risk of OUD in naïve users and risk of relapse in individuals recovering
from OUD. We hypothesize that these clinically important differences in opioid receptor expression and behavior
can be measured by otoendoscopic paired agent imaging (OPAI) of the inner ear. Therefore, we seek R21
funding under the NIBIB “trailblazer” opportunity to: (1) design and assemble a rigid otoendoscope to perform
PAI of opioid binding kinetics in the inner ear, and (2) use otoendoscopic paired agent imaging (OPAI) to quantify
receptor behavior during chronic opioid exposure and following naloxone-induced withdrawal using
fluorescently-labeled opioid peptide agonist/antagonist pairs. The otoendoscope will consist of commercially
available Storz endoscope (<2.5 mm diameter) coupled to a small module that splits the image into three bands
(RGB, 700- and 800- fluorescence) and then transmits to a single sCMOS camera. A multi-LED light source of
specific illumination and excitation bands is transmitted down the endoscope via the Storz light guide coupler.
By the end of the project, we will address three hypotheses: (1) spiral ganglia cells of the inner ear can be imaged
using an otoendoscope in order to quantify binding potential and internalization, (2) binding and internalization
rate predict chron...

## Key facts

- **NIH application ID:** 9850590
- **Project number:** 5R21EB024771-04
- **Recipient organization:** DARTMOUTH-HITCHCOCK CLINIC
- **Principal Investigator:** Jonathan T Elliott
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $185,096
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850590

## Citation

> US National Institutes of Health, RePORTER application 9850590, OTOENDOSCOPE PAIRED AGENT IMAGING OF OPIOID RECEPTOR KINETICS DURING DEPENDENCY AND WITHDRAWAL (5R21EB024771-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9850590. Licensed CC0.

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