Modeling [18F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge
Identifieur interne : 001654 ( Main/Exploration ); précédent : 001653; suivant : 001655Modeling [18F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge
Auteurs : Svetlana Chefer [États-Unis] ; David Thomasson [États-Unis] ; Jurgen Seidel [États-Unis] ; Richard C. Reba [États-Unis] ; J. Kyle Bohannon [États-Unis] ; Mathew G. Lackemeyer [États-Unis] ; Chris Bartos [États-Unis] ; Philip J. Sayre [États-Unis] ; Laura Bollinger [États-Unis] ; Lisa E. Hensley [États-Unis] ; Peter B. Jahrling [États-Unis] ; Reed F. Johnson [États-Unis]Source :
- EJNMMI Research [ 2191-219X ] ; 2015.
Abstract
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 (
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
Two-way repeated measures analysis of variance revealed alterations in
[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.
The online version of this article (doi:10.1186/s13550-015-0143-x) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s13550-015-0143-x
PubMed: 26573211
PubMed Central: 4646887
Affiliations:
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Reba</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.94365.3d</institution-id><institution-id institution-id-type="ISNI">0000000122975165</institution-id><institution>Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center,</institution><institution>National Institutes of Health,</institution></institution-wrap>Bethesda, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Bethesda</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000000121649667</institution-id><institution>Present address: Visiting Scientist, Integrated Research Facility, Division of Clinical Research,</institution><institution>National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution></institution-wrap>Frederick, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Frederick</wicri:cityArea></affiliation></author><author><name sortKey="Bohannon, J Kyle" sort="Bohannon, J Kyle" uniqKey="Bohannon J" first="J. Kyle" last="Bohannon">J. Kyle Bohannon</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000000121649667</institution-id><institution>Integrated Research Facility, Division of Clinical Research,</institution><institution>National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution></institution-wrap>Frederick, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Frederick</wicri:cityArea></affiliation></author><author><name sortKey="Lackemeyer, Mathew G" sort="Lackemeyer, Mathew G" uniqKey="Lackemeyer M" first="Mathew G." last="Lackemeyer">Mathew G. Lackemeyer</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000000121649667</institution-id><institution>Integrated Research Facility, Division of Clinical Research,</institution><institution>National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution></institution-wrap>Frederick, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Frederick</wicri:cityArea></affiliation></author><author><name sortKey="Bartos, Chris" sort="Bartos, Chris" uniqKey="Bartos C" first="Chris" last="Bartos">Chris Bartos</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000000121649667</institution-id><institution>Integrated Research Facility, Division of Clinical Research,</institution><institution>National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution></institution-wrap>Frederick, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Frederick</wicri:cityArea></affiliation></author><author><name sortKey="Sayre, Philip J" sort="Sayre, Philip J" uniqKey="Sayre P" first="Philip J." last="Sayre">Philip J. Sayre</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000000121649667</institution-id><institution>Integrated Research Facility, Division of Clinical Research,</institution><institution>National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution></institution-wrap>Frederick, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Frederick</wicri:cityArea></affiliation></author><author><name sortKey="Bollinger, Laura" sort="Bollinger, Laura" uniqKey="Bollinger L" first="Laura" last="Bollinger">Laura Bollinger</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000000121649667</institution-id><institution>Integrated Research Facility, Division of Clinical Research,</institution><institution>National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution></institution-wrap>Frederick, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Frederick</wicri:cityArea></affiliation></author><author><name sortKey="Hensley, Lisa E" sort="Hensley, Lisa E" uniqKey="Hensley L" first="Lisa E." last="Hensley">Lisa E. Hensley</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000000121649667</institution-id><institution>Integrated Research Facility, Division of Clinical Research,</institution><institution>National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution></institution-wrap>Frederick, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Frederick</wicri:cityArea></affiliation></author><author><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B." last="Jahrling">Peter B. Jahrling</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000000121649667</institution-id><institution>Integrated Research Facility, Division of Clinical Research,</institution><institution>National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution></institution-wrap>Frederick, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Frederick</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000000121649667</institution-id><institution>Emerging Viral Pathogens Section, Division of Intramural Research,</institution><institution>National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution></institution-wrap>Frederick, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Frederick</wicri:cityArea></affiliation></author><author><name sortKey="Johnson, Reed F" sort="Johnson, Reed F" uniqKey="Johnson R" first="Reed F." last="Johnson">Reed F. Johnson</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.419681.3</institution-id><institution-id institution-id-type="ISNI">0000000121649667</institution-id><institution>Emerging Viral Pathogens Section, Division of Intramural Research,</institution><institution>National Institute of Allergy and Infectious Diseases, National Institutes of Health,</institution></institution-wrap>Frederick, MD USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Frederick</wicri:cityArea></affiliation></author></analytic><series><title level="j">EJNMMI Research</title><idno type="eISSN">2191-219X</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p id="Par1">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. <sup>18</sup>F-Fluorodeoxyglucose ([<sup>18</sup>F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [<sup>18</sup>F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [<sup>18</sup>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 (<italic>K</italic><sub><italic>i</italic></sub>) in responsive lymphoid tissue<italic>.</italic></p></sec><sec><title>Methods</title><p id="Par2">Multiple [<sup>18</sup>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 [<sup>18</sup>F]-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate <italic>K</italic><sub><italic>i</italic></sub> for lymphoid tissues by Patlak plot.</p></sec><sec><title>Results</title><p id="Par3">Two-way repeated measures analysis of variance revealed alterations in <italic>K</italic><sub><italic>i</italic></sub> that was associated with the time point (<italic>p</italic> < 0.001) after virus exposure and the location of lymphoid tissue (<italic>p</italic> = 0.0004). As revealed by a statistically significant interaction (<italic>p</italic> < 0.0001) between these two factors, the pattern of <italic>K</italic><sub><italic>i</italic></sub> changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in <italic>K</italic><sub><italic>i</italic></sub> was observed in mediastinal lymph nodes (LNs) that correlated to <italic>K</italic><sub><italic>i</italic></sub> changes in axillary LNs. Changes in LNs <italic>K</italic><sub><italic>i</italic></sub> were concurrent with elevations of monocytes in peripheral blood.</p></sec><sec><title>Conclusions</title><p id="Par4">[<sup>18</sup>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.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/s13550-015-0143-x) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Feldmann, F" uniqKey="Feldmann F">F Feldmann</name></author><author><name sortKey="Rasmussen, Al" uniqKey="Rasmussen A">AL Rasmussen</name></author><author><name sortKey="Okumura, A" uniqKey="Okumura A">A Okumura</name></author><author><name sortKey="Peng, X" uniqKey="Peng X">X Peng</name></author><author><name sortKey="Thomas, Mj" 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first="Svetlana" last="Chefer">Svetlana Chefer</name></region><name sortKey="Bartos, Chris" sort="Bartos, Chris" uniqKey="Bartos C" first="Chris" last="Bartos">Chris Bartos</name><name sortKey="Bohannon, J Kyle" sort="Bohannon, J Kyle" uniqKey="Bohannon J" first="J. Kyle" last="Bohannon">J. Kyle Bohannon</name><name sortKey="Bollinger, Laura" sort="Bollinger, Laura" uniqKey="Bollinger L" first="Laura" last="Bollinger">Laura Bollinger</name><name sortKey="Hensley, Lisa E" sort="Hensley, Lisa E" uniqKey="Hensley L" first="Lisa E." last="Hensley">Lisa E. Hensley</name><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B." last="Jahrling">Peter B. Jahrling</name><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B." last="Jahrling">Peter B. Jahrling</name><name sortKey="Johnson, Reed F" sort="Johnson, Reed F" uniqKey="Johnson R" first="Reed F." last="Johnson">Reed F. Johnson</name><name sortKey="Lackemeyer, Mathew G" sort="Lackemeyer, Mathew G" uniqKey="Lackemeyer M" first="Mathew G." last="Lackemeyer">Mathew G. Lackemeyer</name><name sortKey="Reba, Richard C" sort="Reba, Richard C" uniqKey="Reba R" first="Richard C." last="Reba">Richard C. Reba</name><name sortKey="Reba, Richard C" sort="Reba, Richard C" uniqKey="Reba R" first="Richard C." last="Reba">Richard C. Reba</name><name sortKey="Sayre, Philip J" sort="Sayre, Philip J" uniqKey="Sayre P" first="Philip J." last="Sayre">Philip J. Sayre</name><name sortKey="Seidel, Jurgen" sort="Seidel, Jurgen" uniqKey="Seidel J" first="Jurgen" last="Seidel">Jurgen Seidel</name><name sortKey="Thomasson, David" sort="Thomasson, David" uniqKey="Thomasson D" first="David" last="Thomasson">David Thomasson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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