Mannes, Philip
(2023)
Molecular imaging of chemokine-like receptor 1 (CMKLR1) for non-invasive monitoring of monocyte-derived macrophages in experimental lung injury and remodeling.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
There is a lack of techniques for noninvasive imaging of pulmonary inflammation associated
with acute lung injury and pulmonary fibrosis. Here we determined the potential of positron
emission tomography of chemokine-like receptor 1 (CMKLR1) to monitor pulmonary
inflammation in murine models of lipopolysaccharide- and bleomycin-induced lung injury. Lung
uptake of our recently described CMKLR1-targeting radiotracer, [64Cu]NODAGA-CG34, was
increased in both models during the inflammatory phase of lung injury and corresponded to lung
regions with high CMKLR1 expression. Monocyte-derived macrophages, and to a lesser extent
interstitial macrophages and natural killer cells, were the predominant CMKLR1 expressing
leukocytes in the lungs, and the pattern of CMKLR1 expression closely resembled that of the
radiotracer uptake. Additionally, we establish the clinical relevance of CMKLR1 as a biomarker
of ongoing pulmonary inflammation by demonstrating expression of CMKLR1 among patients
with acute respiratory distress syndrome (e.g., COVID-19) and pulmonary fibrosis resulting from
multiple etiologies. Furthermore, we show that pulmonary expression of CMKLR1 may provide
prognostic information in patients with pulmonary fibrosis. CMKLR1-PET is a promising
approach to monitor the dynamics of lung inflammation and may represent a new approach for
endotyping patients with inflammatory lung diseases.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Committee Chair | Villanueva, Flordeliza | | | | | Thesis Advisor | Tavakoli, Sina | | | | | Committee Member | Lee, Janet | | | | | Committee Member | Kliment, Corrine | | | | | Committee Member | Nedrow, Jessie | | | | | Committee Member | Panigrahy, Ashok | | | |
|
| Date: |
8 December 2023 |
| Date Type: |
Publication |
| Defense Date: |
2 June 2023 |
| Approval Date: |
8 December 2023 |
| Submission Date: |
1 August 2023 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
203 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Cellular and Molecular Pathology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Macrophage, CMKLR1, acute lung injury, lung fibrosis |
| Date Deposited: |
08 Dec 2023 14:55 |
| Last Modified: |
08 Dec 2023 14:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/44943 |
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