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EJNMMI Research
Published in: EJNMMI Research 1/2015

Open Access 01-12-2015 | Original research

Modeling [18F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge

Authors: Svetlana Chefer, David Thomasson, Jurgen Seidel, Richard C. Reba, J. Kyle Bohannon, Mathew G. Lackemeyer, Chris Bartos, Philip J. Sayre, Laura Bollinger, Lisa E. Hensley, Peter B. Jahrling, Reed F. Johnson

Published in: EJNMMI Research | Issue 1/2015

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Abstract

Background

The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. 18F-Fluorodeoxyglucose ([18F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [18F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [18F]-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (K i ) in responsive lymphoid tissue.

Methods

Multiple [18F]-FDG-PET and CT images were acquired on a PET/CT clinical scanner modified to operate in a biosafety level 4 environment prior to and up to 29 days after MERS-CoV aerosol exposure. Time activity curves of various lymphoid tissues were reconstructed to follow the [18F]-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate K i for lymphoid tissues by Patlak plot.

Results

Two-way repeated measures analysis of variance revealed alterations in K i that was associated with the time point (p < 0.001) after virus exposure and the location of lymphoid tissue (p = 0.0004). As revealed by a statistically significant interaction (p < 0.0001) between these two factors, the pattern of K i changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in K i was observed in mediastinal lymph nodes (LNs) that correlated to K i changes in axillary LNs. Changes in LNs K i were concurrent with elevations of monocytes in peripheral blood.

Conclusions

[18F]-FDG-PET is able to detect subtle changes in host immune response to contain a subclinical virus infection. Full quantitative analysis is the preferred approach rather than semiquantitative analysis using standardized uptake value for detection of the immune response to the virus.
Appendix
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Metadata
Title
Modeling [18F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge
Authors
Svetlana Chefer
David Thomasson
Jurgen Seidel
Richard C. Reba
J. Kyle Bohannon
Mathew G. Lackemeyer
Chris Bartos
Philip J. Sayre
Laura Bollinger
Lisa E. Hensley
Peter B. Jahrling
Reed F. Johnson
Publication date
01-12-2015
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2015
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-015-0143-x

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