# Adenosine A2 Receptors and Imaging of Inflammation in Lung Reperfusion Injury

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $658,089

## Abstract

Project Summary
Ischemia-reperfusion injury (IRI), which leads to primary graft dysfunction (PGD), is a
major source of early mortality after lung transplantation. Current clinical methods to
diagnose PGD are limited to chest x-ray, CT, and functional tests, none of which
specifically address acute inflammation or immune cell activation; key components of
lung IRI. FDG-PET imaging is often used clinically as an indication of inflammation and
neutrophil activity; however, FDG-PET is non-specific by imaging general metabolic
activity. The primary objective of this proposal is to develop novel, cell-specific SPECT
imaging methods to provide sensitive and early diagnosis of IRI after lung
transplantation. Using a murine model of lung IRI, Aim 1 will validate three novel
molecular probes for SPECT imaging of lung IRI: 99mTc-cFLFLF that targets formyl
peptide receptor on activated neutrophils, 99mTc-EC20 that targets activated, pro-
inflammatory M1 macrophages, and 99mTc-labeled anti-mannose receptor Nanobodies
that target alternatively activated, anti-inflammatory M2 macrophages. We hypothesize
that targeting of M1 macrophages will provide the earliest diagnosis of IRI prior to
manifestation of PGD while targeting of M2 macrophages will allow informative
assessment of the resolution of IRI via immunosuppressive actions. SPECT imaging
with these probes will be compared to FDG-PET imaging. Aim 2 will use SPECT imaging
in mice to monitor the response to adenosine receptor-targeted therapies aimed at
attenuating IRI. Attenuation of IRI by adenosine A2A receptor (A2AR) agonism and/or
A2BR antagonism will be focused on, and alveolar epithelial mechanisms for A2BR
antagonist-mediated protection from IRI will be determined. Aim 3 will translate our
results to a clinically relevant, large animal lung transplant model by determining if
SPECT imaging will provide early diagnosis of lung IRI after transplantation of porcine
lungs. The successful completion of our proposal could result in translation of these
novel imaging methods to the clinical setting with the goal of providing an effective, non-
invasive means for early diagnosis of IRI in order to permit rapid, targeted therapeutic
interventions to prevent PGD and thus improve short- and long-term outcomes in lung
transplant recipients.

## Key facts

- **NIH application ID:** 9851913
- **Project number:** 5R01HL130053-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Irving L. Kron
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $658,089
- **Award type:** 5
- **Project period:** 2017-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851913

## Citation

> US National Institutes of Health, RePORTER application 9851913, Adenosine A2 Receptors and Imaging of Inflammation in Lung Reperfusion Injury (5R01HL130053-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851913. Licensed CC0.

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