Assessing organ-level immunoreactivity in a rat model of sepsis using TSPO PET imaging

• Published in: Frontiers in immunology 2022-11, Vol.13, p.1010263-1010263
• Main Authors: Martinez-Orengo, Neysha, Tahmazian, Sarine, Lai, Jianhao, Wang, Zeping, Sinharay, Sanhita, Schreiber-Stainthorp, William, Basuli, Falguni, Maric, Dragan, Reid, William, Shah, Swati, Hammoud, Dima A.
• Format: Article
• Language: English
• Subjects: 18F-DPA-714; Immunology; organ-level immunoreactivity; sepsis; TSPO (18 kda translocator protein); whole body PET/CT
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.1010263

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, [ 18 F]DPA-714, as a biomarker for reactive immunoreactive changes in the brain and peripheral organs. In vivo dynamic PET/CT scans showed increased [ 18 F]DPA-714 binding in the brain, lungs, liver and bone marrow, 4 hours after LPS injection. Post-LPS mean standard uptake values (SUV mean) at equilibrium were significantly higher in those organs compared to baseline. Changes in spleen [ 18 F]DPA-714 binding were variable but generally decreased after LPS. SUV mean 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 [ 18 F]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 .