Novel application of [18F]DPA714 for visualizing the lower respiratory tract of SARS-CoV-2-exposed rhesus monkeys

ABSTRACT

Aim/Introduction: A hallmark of coronavirus disease 2019 (COVID-19) is lower respiratory tract infection and pneumonia. Infection of nonhuman primates mirrors mild-to-moderate human disease determined with concordant immunologic, virologic, and lung histopathologic findings in combination with imaging abnormalities. Particularly in the lower respiratory tract, medical imaging of pulmonary disease contributes uniquely to the understanding and measuring of the consequences of an infection. Advanced medical imaging, such as PET-CT, of the lungs of SARS-CoV-2-exposed nonhuman primates shows great promise in detecting and longitudinally evaluating disease in a non-invasive manner. The aim of this study was to investigate the application of [18F]DPA714 for visualizing the inflammation processes in the lungs of SARS-CoV-2-infected rhesus monkeys. Material(s) and Method(s) Four experimentally SARS-CoV-2 infected rhesus monkeys were followed for seven weeks post infection (pi) with a weekly PETCT using a MultiScan Large Field of View Extreme Resolution Research Imager (LFER) 150 (Mediso Medical Imaging Systems Ltd., Budapest, Hungary) with [18F]DPA714 as radiotracer. Following a retrospectively gated CT, an intravenous bolus of approximately 180 MBq [18F]DPA714 (molar activity 77.4 GBq/mumol (range 39.8- 150.6 GBq/mumol, radioactivity concentration of 277.0+/-172.8 MBq/ mL, a radiochemical purity > 98.0%) was administered. Two PET images, ten minutes each, of a single field-of-view covering the chest area, were obtained ten and thirty minutes after injection. To confirm the infection of SARS-CoV-2 , both nasal and tracheal swabs and blood samples were obtained. Result(s) All animals tested positive for SARS-CoV-2 in both swabs on multiple timepoints pi. The initial development of pulmonary lesions was already detected at the first scan 2-days pi. PET revealed an increased tracer uptake in the pulmonary lesions and mediastinal lymph nodes of all animals starting from the first scan pi onwards. However, also an increased uptake was detected in the lung tissue surrounding the lesions, which persisted until day 30 and then subsided by day 37-44 pi. In parallel, a similar pattern of increased expression of activation markers was observed on dendritic cells in blood. Conclusion(s) This study illustrates that [18F]DPA714 is a valuable radiotracer to visualize SARS-CoV-2-associated pulmonary inflammation even during mild-to-moderate disease. In addition, the inflammatory process detected in anatomically unaffected lung tissue coincided with dendritic cell activation detected in blood samples. Our data indicate that [18F]DPA714 can be applied to visualize the pulmonary tract following a SARS-CoV-2 infection in rhesus monkeys and may be translated to the clinic as diagnostic tracer for this indication too.