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Towards precision medicine in COPD: bioradiomic SPECT-CT quantification of active lung inflammation

Towards precision medicine in COPD: bioradiomic SPECT-CT quantification of active lung inflammation
Towards precision medicine in COPD: bioradiomic SPECT-CT quantification of active lung inflammation
Introduction: multiple inflammatory endotypes exist as targets for therapy in COPD but novel precision medicine approaches are needed to define these. We aim to develop non-invasive imaging methods to quantify specific inflammatory cytokines in the lung as potential targets for therapy.

Methods: using SPECT-CT, we developed techniques to quantify cytokine activity. Five patients with COPD and 5 healthy volunteers were recruited and gave informed consent. They underwent SPECT-CT of the lungs at 6 (+/- 1) and 24 (+/- 4) hours after infusion of 99mTc-anti-TNF-α to quantify TNF-α activity in the lungs. Quantification (figure 1) was normalised to aortic arch signal to account for biological clearance.

Results: isotope signals were quantified at 6 and 24 hours. Median normalised lung SPECT counts (CN) were higher in the healthy group at both time points. However, the increase in CN at 24 hours calculated as a percentage of the 6-hour scan (a measure of tissue bound signal) was higher in the COPD group at 64.88% +/- (SD) 31.04 compared with 35.38% +/- 34.33 in the healthy group - a significant change in the COPD group (p=0.029, paired t-test) but not the healthy.

Conclusions: this proof-of-concept study provides early evidence that molecular imaging of inflammatory cytokines is possible in the lungs of patients with COPD.
0903-1936
Welham, Benjamin
2606c253-7562-45e6-a284-26a9915d35bf
Bennett, Michael
6df5585a-3d93-4870-8797-389759fc82c7
Ostridge, Kristoffer
d2271bae-b078-4390-8919-8f8c0e20542c
Guy, Matthew
473bbb88-641b-40a5-b22d-221bc048eeb5
Zvavamwe, Clint
a7537da6-3b05-47a7-8711-6ba3e5869ca9
Sundram, Francis
2ab8eac4-6081-4acb-a9b9-d6b9274aba05
Wilkinson, Tom
8c55ebbb-e547-445c-95a1-c8bed02dd652
Welham, Benjamin
2606c253-7562-45e6-a284-26a9915d35bf
Bennett, Michael
6df5585a-3d93-4870-8797-389759fc82c7
Ostridge, Kristoffer
d2271bae-b078-4390-8919-8f8c0e20542c
Guy, Matthew
473bbb88-641b-40a5-b22d-221bc048eeb5
Zvavamwe, Clint
a7537da6-3b05-47a7-8711-6ba3e5869ca9
Sundram, Francis
2ab8eac4-6081-4acb-a9b9-d6b9274aba05
Wilkinson, Tom
8c55ebbb-e547-445c-95a1-c8bed02dd652

Welham, Benjamin, Bennett, Michael, Ostridge, Kristoffer, Guy, Matthew, Zvavamwe, Clint, Sundram, Francis and Wilkinson, Tom (2023) Towards precision medicine in COPD: bioradiomic SPECT-CT quantification of active lung inflammation. European Respiratory Journal, 62 (Suppl. 67), [OA4856]. (doi:10.1183/13993003.congress-2023.OA4856).

Record type: Article

Abstract

Introduction: multiple inflammatory endotypes exist as targets for therapy in COPD but novel precision medicine approaches are needed to define these. We aim to develop non-invasive imaging methods to quantify specific inflammatory cytokines in the lung as potential targets for therapy.

Methods: using SPECT-CT, we developed techniques to quantify cytokine activity. Five patients with COPD and 5 healthy volunteers were recruited and gave informed consent. They underwent SPECT-CT of the lungs at 6 (+/- 1) and 24 (+/- 4) hours after infusion of 99mTc-anti-TNF-α to quantify TNF-α activity in the lungs. Quantification (figure 1) was normalised to aortic arch signal to account for biological clearance.

Results: isotope signals were quantified at 6 and 24 hours. Median normalised lung SPECT counts (CN) were higher in the healthy group at both time points. However, the increase in CN at 24 hours calculated as a percentage of the 6-hour scan (a measure of tissue bound signal) was higher in the COPD group at 64.88% +/- (SD) 31.04 compared with 35.38% +/- 34.33 in the healthy group - a significant change in the COPD group (p=0.029, paired t-test) but not the healthy.

Conclusions: this proof-of-concept study provides early evidence that molecular imaging of inflammatory cytokines is possible in the lungs of patients with COPD.

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e-pub ahead of print date: 27 October 2023

Identifiers

Local EPrints ID: 486229
URI: http://eprints.soton.ac.uk/id/eprint/486229
ISSN: 0903-1936
PURE UUID: 426c140d-7fd6-48e5-a911-9e92334d96a8

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Date deposited: 15 Jan 2024 17:36
Last modified: 17 Mar 2024 06:50

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Contributors

Author: Benjamin Welham
Author: Michael Bennett
Author: Kristoffer Ostridge
Author: Matthew Guy
Author: Clint Zvavamwe
Author: Francis Sundram
Author: Tom Wilkinson

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