Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging
There is current need for new approaches to assess/measure organ-level immunoreactivity and ensuing dysfunction in systemic inflammatory response syndrome (SIRS) and sepsis, in order to protect or recover organ function. Using a rat model of systemic sterile inflammatory shock (intravenous LPS admin...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1010263/full |
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| author | Neysha Martinez-Orengo Sarine Tahmazian Jianhao Lai Zeping Wang Sanhita Sinharay William Schreiber-Stainthorp Falguni Basuli Dragan Maric William Reid Swati Shah Dima A. Hammoud |
| author_facet | Neysha Martinez-Orengo Sarine Tahmazian Jianhao Lai Zeping Wang Sanhita Sinharay William Schreiber-Stainthorp Falguni Basuli Dragan Maric William Reid Swati Shah Dima A. Hammoud |
| author_sort | Neysha Martinez-Orengo |
| collection | DOAJ |
| description | There is current need for new approaches to assess/measure organ-level immunoreactivity and ensuing dysfunction in systemic inflammatory response syndrome (SIRS) and sepsis, in order to protect or recover organ function. Using a rat model of systemic sterile inflammatory shock (intravenous LPS administration), we performed PET imaging with a translocator protein (TSPO) tracer, [18F]DPA-714, as a biomarker for reactive immunoreactive changes in the brain and peripheral organs. In vivo dynamic PET/CT scans showed increased [18F]DPA-714 binding in the brain, lungs, liver and bone marrow, 4 hours after LPS injection. Post-LPS mean standard uptake values (SUVmean) at equilibrium were significantly higher in those organs compared to baseline. Changes in spleen [18F]DPA-714 binding were variable but generally decreased after LPS. SUVmean values in all organs, except the spleen, positively correlated with several serum cytokines/chemokines. In vitro measures of TSPO expression and immunofluorescent staining validated the imaging results. Noninvasive molecular imaging with [18F]DPA-714 PET in a rat model of systemic sterile inflammatory shock, along with in vitro measures of TSPO expression, showed brain, liver and lung inflammation, spleen monocytic efflux/lymphocytic activation and suggested increased bone marrow hematopoiesis. TSPO PET imaging can potentially be used to quantify SIRS and sepsis-associated organ-level immunoreactivity and assess the effectiveness of therapeutic and preventative approaches for associated organ failures, in vivo. |
| first_indexed | 2024-04-12T10:41:10Z |
| format | Article |
| id | doaj.art-2512f36b07e448e9b9e028795ea14033 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T10:41:10Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2512f36b07e448e9b9e028795ea140332022-12-22T03:36:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10102631010263Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imagingNeysha Martinez-Orengo0Sarine Tahmazian1Jianhao Lai2Zeping Wang3Sanhita Sinharay4William Schreiber-Stainthorp5Falguni Basuli6Dragan Maric7William Reid8Swati Shah9Dima A. Hammoud10Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesCenter for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesCenter for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesCenter for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesCenter for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesCenter for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesChemistry and Synthesis Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD, United StatesFlow and Imaging Cytometry Core Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United StatesCenter for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesCenter for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesCenter for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesThere is current need for new approaches to assess/measure organ-level immunoreactivity and ensuing dysfunction in systemic inflammatory response syndrome (SIRS) and sepsis, in order to protect or recover organ function. Using a rat model of systemic sterile inflammatory shock (intravenous LPS administration), we performed PET imaging with a translocator protein (TSPO) tracer, [18F]DPA-714, as a biomarker for reactive immunoreactive changes in the brain and peripheral organs. In vivo dynamic PET/CT scans showed increased [18F]DPA-714 binding in the brain, lungs, liver and bone marrow, 4 hours after LPS injection. Post-LPS mean standard uptake values (SUVmean) at equilibrium were significantly higher in those organs compared to baseline. Changes in spleen [18F]DPA-714 binding were variable but generally decreased after LPS. SUVmean values in all organs, except the spleen, positively correlated with several serum cytokines/chemokines. In vitro measures of TSPO expression and immunofluorescent staining validated the imaging results. Noninvasive molecular imaging with [18F]DPA-714 PET in a rat model of systemic sterile inflammatory shock, along with in vitro measures of TSPO expression, showed brain, liver and lung inflammation, spleen monocytic efflux/lymphocytic activation and suggested increased bone marrow hematopoiesis. TSPO PET imaging can potentially be used to quantify SIRS and sepsis-associated organ-level immunoreactivity and assess the effectiveness of therapeutic and preventative approaches for associated organ failures, in vivo.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1010263/fullsepsisTSPO (18 kda translocator protein)18F-DPA-714whole body PET/CTorgan-level immunoreactivity |
| spellingShingle | Neysha Martinez-Orengo Sarine Tahmazian Jianhao Lai Zeping Wang Sanhita Sinharay William Schreiber-Stainthorp Falguni Basuli Dragan Maric William Reid Swati Shah Dima A. Hammoud Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging Frontiers in Immunology sepsis TSPO (18 kda translocator protein) 18F-DPA-714 whole body PET/CT organ-level immunoreactivity |
| title | Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging |
| title_full | Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging |
| title_fullStr | Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging |
| title_full_unstemmed | Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging |
| title_short | Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging |
| title_sort | assessing organ level immunoreactivity in a rat model of sepsis using tspo pet imaging |
| topic | sepsis TSPO (18 kda translocator protein) 18F-DPA-714 whole body PET/CT organ-level immunoreactivity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1010263/full |
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