TY - JOUR
T1 - Novel application of [18F]DPA714 for visualizing the pulmonary inflammation process of SARS-CoV-2-infection in rhesus monkeys (Macaca mulatta)
AU - Meijer, Lisette
AU - Böszörményi, Kinga P
AU - Bakker, Jaco
AU - Koopman, Gerrit
AU - Mooij, Petra
AU - Verel, Dagmar
AU - Fagrouch, Zahra
AU - Verstrepen, Babs E
AU - Funke, Uta
AU - Mooijer, Martien P J
AU - Langermans, J.A.M.
AU - Verschoor, Ernst J
AU - Windhorst, Albert D
AU - Stammes, Marieke A
N1 - Funding Information:
The authors have no relevant financial or non-financial interests to disclose. Part of this work was supported by internal funding from the Biomedical Primate Research Centre. ADW is editor-in-chief of Nuclear Medicine and Biology and was not involved in the review of this manuscript. This publication was supported by the European Virus Archive GLOBAL (EVA-GLOBAL) project that has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 87L029 . KPB was supported by the European Union's Marie Skłodowska-Curie Innovative Training Network HONOURs ; grant agreement no. 721367 .
Publisher Copyright:
© 2022 The Authors
PY - 2022/9/1
Y1 - 2022/9/1
N2 - RATIONALE: The aim of this study was to investigate the application of [18F]DPA714 to visualize the inflammation process in the lungs of SARS-CoV-2-infected rhesus monkeys, focusing on the presence of pulmonary lesions, activation of mediastinal lymph nodes and surrounded lung tissue.METHODS: Four experimentally SARS-CoV-2 infected rhesus monkeys were followed for seven weeks post infection (pi) with a weekly PET-CT using [18F]DPA714. Two PET images, 10 min each, of a single field-of-view covering the chest area, were obtained 10 and 30 min after injection. To determine the infection process swabs, blood and bronchoalveolar lavages (BALs) were obtained.RESULTS: All animals were positive for SARS-CoV-2 in both the swabs and BALs on multiple timepoints pi. The initial development of pulmonary lesions was already detected at the first scan, performed 2-days pi. PET revealed an increased tracer uptake in the pulmonary lesions and mediastinal lymph nodes of all animals from the first scan obtained after infection and 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.PRINCIPAL CONCLUSIONS: This study illustrates that [18F]DPA714 is a valuable radiotracer to visualize SARS-CoV-2-associated pulmonary inflammation, which coincided with activation of dendritic cells in blood. [18F]DPA714 thus has the potential to be of added value as diagnostic tracer for other viral respiratory infections.
AB - RATIONALE: The aim of this study was to investigate the application of [18F]DPA714 to visualize the inflammation process in the lungs of SARS-CoV-2-infected rhesus monkeys, focusing on the presence of pulmonary lesions, activation of mediastinal lymph nodes and surrounded lung tissue.METHODS: Four experimentally SARS-CoV-2 infected rhesus monkeys were followed for seven weeks post infection (pi) with a weekly PET-CT using [18F]DPA714. Two PET images, 10 min each, of a single field-of-view covering the chest area, were obtained 10 and 30 min after injection. To determine the infection process swabs, blood and bronchoalveolar lavages (BALs) were obtained.RESULTS: All animals were positive for SARS-CoV-2 in both the swabs and BALs on multiple timepoints pi. The initial development of pulmonary lesions was already detected at the first scan, performed 2-days pi. PET revealed an increased tracer uptake in the pulmonary lesions and mediastinal lymph nodes of all animals from the first scan obtained after infection and 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.PRINCIPAL CONCLUSIONS: This study illustrates that [18F]DPA714 is a valuable radiotracer to visualize SARS-CoV-2-associated pulmonary inflammation, which coincided with activation of dendritic cells in blood. [18F]DPA714 thus has the potential to be of added value as diagnostic tracer for other viral respiratory infections.
KW - TSPO
KW - Pulmonary inflammation
KW - PET-CT
KW - COVID-19
KW - Nonhuman primates
UR - http://www.scopus.com/inward/record.url?scp=85131575553&partnerID=8YFLogxK
U2 - 10.1016/j.nucmedbio.2022.05.002
DO - 10.1016/j.nucmedbio.2022.05.002
M3 - Article
C2 - 35660200
SN - 0969-8051
VL - 112-113
SP - 1
EP - 8
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
ER -