PET imaging of TSPO expression in immune cells can assess organ-level pathophysiology in high-consequence viral infections

Author:

Shah Swati1,Sinharay Sanhita1,Patel Reema1ORCID,Solomon Jeffrey2ORCID,Lee Ji Hyun3ORCID,Schreiber-Stainthorp William1ORCID,Basuli Falguni4ORCID,Zhang Xiang4ORCID,Hagen Katie R.3ORCID,Reeder Rebecca3,Wakim Paul5ORCID,Huzella Louis M.3,Maric Dragan6ORCID,Johnson Reed F.7,Hammoud Dima A.1

Affiliation:

1. Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, MD 20892

2. Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702

3. Integrated Research Facility, National Institute of Allergy and Infectious Diseases, NIH, Frederick, MD 21702

4. Chemistry and Synthesis Center, National Heart, Lung, and Blood Institute, NIH, Rockville, MD 20824

5. Biostatistics and Clinical Epidemiology Service, Clinical Center, NIH, Bethesda, MD 20892

6. Flow and Imaging Cytometry Core Facility, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892

7. Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, NIH, Frederick, MD 21702

Abstract

Significance Ebola virus (EBOV) infection is a severe, often fatal disease with poorly understood pathophysiology. Here, we performed [ 18 F]-DPA-714 Positron Emission Tomography (PET) in a macaque model of EBOV infection to longitudinally track and quantify the translocator protein (TSPO), an immune cell marker. The imaging findings, along with immunohistology and other disease markers, showed increasing stem cell proliferation in the bone marrow, along with progressive monocytic and lymphocytic loss in the spleen and lungs. This study provides real-time noninvasive assessment of EBOV pathogenesis and disease progression, as well as the associated host responses, at the organ level. This approach can be similarly used to study other inflammatory and infectious diseases and to test the efficacy of newly developed therapeutics and vaccines.

Funder

Intramural research program, NIH

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Reference53 articles.

1. World Health Organization Ebola situation report 2016. https://apps.who.int/ebola/current-situation/ebola-situation-report-30-march-2016.

2. Centers for Disease Control 2021 Democratic Republic of the Congo North Kivu Province. https://www.cdc.gov/vhf/ebola/outbreaks/drc/2021-february.html (Accessed 23 March 2022).

3. World Health Organization Ebola—Guinea” (17 February 2021). https://www.who.int/emergencies/disease-outbreak-news/item/2021-DON312 (Accessed 23 March 2022).

4. Filovirus Tropism: Cellular Molecules for Viral Entry

5. Transmission of Ebola Hemorrhagic Fever: A Study of Risk Factors in Family Members, Kikwit, Democratic Republic of the Congo, 1995

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