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

• Published in: EJNMMI research Vol. 5; no. 1; pp. 65 - 11
• Main Authors: Chefer, Svetlana, Thomasson, David, Seidel, Jurgen, Reba, Richard C., Bohannon, J. Kyle, Lackemeyer, Mathew G., Bartos, Chris, Sayre, Philip J., Bollinger, Laura, Hensley, Lisa E., Jahrling, Peter B., Johnson, Reed F.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 16-11-2015; Springer Nature B.V
• Subjects: Cardiac Imaging; Coronavirus; Imaging; Medicine; Medicine & Public Health; Nuclear Medicine; Oncology; Original Research; Orthopedics; Radiology; Animal models; MERS-CoV; [; Kinetic modeling; F]-FDG-PET; [18F]-FDG-PET
• ISSN: 2191-219X; 2191-219X
• DOI: 10.1186/s13550-015-0143-x

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.
18
F-Fluorodeoxyglucose ([
18
F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [
18
F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [
18
F]-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 [
18
F]-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 [
18
F]-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
[
18
F]-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.