PET Imaging of Translocator Protein as a Marker of Malaria-Associated Lung Inflammation

• Published in: Infection and immunity 2021-09, Vol.89 (10), p.e0002421-e0002421
• Main Authors: Goggi, Julian L, Claser, Carla, Hartimath, Siddesh V, Hor, Pei Xiang, Tan, Peng Wen, Ramasamy, Boominathan, Abdul Rahman, Husaini, Cheng, Peter, Chang, Zi Wei, Nguee, Samantha Yee Teng, Tang, Jun Rong, Robins, Edward G, Renia, Laurent
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers - metabolism; Disease Models, Animal; Fungal and Parasitic Infections; Immunology; Leukocytes - metabolism; Lung - metabolism; Macrophages - metabolism; Malaria - metabolism; Male; Mice; Mice, Inbred C57BL; Monocytes - metabolism; Plasmodium berghei - pathogenicity; Pneumonia - metabolism; Positron-Emission Tomography - methods; Respiratory Distress Syndrome - metabolism
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00024-21

Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a severe complication of malaria that occurs despite effective antimalarial treatment. Currently, noninvasive imaging procedures such as chest X-rays are used to assess edema in established MA-ARDS, but earlier detection methods are needed to reduce morbidity and mortality. The early stages of MA-ARDS are characterized by the infiltration of leukocytes, in particular monocytes/macrophages; thus, monitoring of immune infiltrates may provide a useful indicator of early pathology. In this study, Plasmodium berghei ANKA-infected C57BL/6 mice, a rodent model of MA-ARDS, were longitudinally imaged using the 18-kDa translocator protein (TSPO) imaging agent [ F]FEPPA as a marker of macrophage accumulation during the development of pathology and in response to combined artesunate and chloroquine diphosphate (ART+CQ) therapy. [ F]FEPPA uptake was compared to blood parasitemia levels and to levels of pulmonary immune cell infiltrates by using flow cytometry. Infected animals showed rapid increases in lung retention of [ F]FEPPA, correlating well with increases in blood parasitemia and pulmonary accumulation of interstitial inflammatory macrophages and major histocompatibility complex class II (MHC-II)-positive alveolar macrophages. Treatment with ART+CQ abrogated this increase in parasitemia and significantly reduced both lung uptake of [ F]FEPPA and levels of macrophage infiltrates. We conclude that retention of [ F]FEPPA in the lungs is well correlated with changes in blood parasitemia and levels of lung-associated macrophages during disease progression and in response to ART+CQ therapy. With further development, TSPO biomarkers may have the potential to accurately assess the early onset of MA-ARDS.