# Molecular Imaging of the ChemR23-Chemerin Axis in Acute Lung Injury

> **NIH NIH F30** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $53,974

## Abstract

Project Summary
Acute lung injury (ALI), clinically known as acute respiratory distress syndrome (ARDS), is a severe and
potentially life-threatening condition with different sub-phenotypes leading to distinct clinical outcomes. In
particular, patients with non-resolving pulmonary inflammation who survive the acute phase of ARDS are a
subpopulation at increased risk for poor outcomes, including long term lung damage and significantly decreased
quality of life. Therefore, developing strategies to monitor ongoing lung inflammation based on inflammatory
signatures (i.e. specific inflammatory mediators and individual immune cell populations) represents a Precision
Medicine approach, especially relevant given the growing development and applications of immunomodulatory
therapies. Molecular imaging using positron emission tomography (PET) is emerging as a promising non-
invasive approach that can used to visualize inflammatory processes and provide prognostic information. Current
PET tracers, primarily 18F-FDG, for lung inflammation suffer from a lack of specificity and poor kinetics. We
propose developing PET tracers targeting the receptor/chemokine ChemR23/chemerin, a newly established
biomarker for imaging lung inflammation. We have designed two classes of PET tracers, an “active” probe
imaging the expression of ChemR23 and an “activatable” probe imaging the inflammatory-protease bioactivation
of the ChemR23-chemerin axis. Our central hypothesis is that modification of the “active” tracer into an
“activatable” tracer through addition of a cleavable C-terminal tail will enhance the specificity of imaging the
ChemR23-chemerin axis by mimicking the local bioactivation and ultimately uptake of chemerin in the
inflammatory environment. We propose two specific aims: SPECIFIC AIM 1: To synthesize and biologically
characterize active and protease-activatable chemerin-derived radiotracers. SPECIFIC AIM 2: To determine the
biological, biochemical, and histological correlates of ChemR23-targeted PET by “active” and “activatable”
tracers in a mouse model of ALI. Our ultimate goal is to develop bioactivatable PET tracers for precision medicine
imaging of ongoing lung injury and inflammation along the ChemR23-chemerin axis to improve research and
clinical prognostic tools.

## Key facts

- **NIH application ID:** 10830975
- **Project number:** 5F30HL158038-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Philip Zachary Mannes
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2021-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10830975

## Citation

> US National Institutes of Health, RePORTER application 10830975, Molecular Imaging of the ChemR23-Chemerin Axis in Acute Lung Injury (5F30HL158038-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10830975. Licensed CC0.

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