Novel application of [18F]DPA714 for visualizing the pulmonary inflammation process of SARS-CoV-2-infection in rhesus monkeys (Macaca mulatta)

Lisette Meijer; Kinga P Böszörményi; Jaco Bakker; Gerrit Koopman; Petra Mooij; Dagmar Verel; Zahra Fagrouch; Babs E Verstrepen; Uta Funke; Martien P J Mooijer; J.A.M. Langermans; Ernst J Verschoor; Albert D Windhorst; Marieke A Stammes

doi:10.1016/j.nucmedbio.2022.05.002

Novel application of [18F]DPA714 for visualizing the pulmonary inflammation process of SARS-CoV-2-infection in rhesus monkeys (Macaca mulatta)

Lisette Meijer
, Kinga P Böszörményi
, Jaco Bakker
, Gerrit Koopman
, Petra Mooij
, Dagmar Verel
, Zahra Fagrouch
, Babs E Verstrepen
, Uta Funke
, Martien P J Mooijer
, J.A.M. Langermans
, Ernst J Verschoor
, Albert D Windhorst
, Marieke A Stammes

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1-8
Number of pages	8
Journal	Nuclear Medicine and Biology
Volume	112-113
Early online date	29 May 2022
DOIs	https://doi.org/10.1016/j.nucmedbio.2022.05.002
Publication status	Published - 1 Sept 2022

Bibliographical note

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

Keywords

TSPO
Pulmonary inflammation
PET-CT
COVID-19
Nonhuman primates

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Meijer, L., Böszörményi, K. P., Bakker, J., Koopman, G., Mooij, P., Verel, D., Fagrouch, Z., Verstrepen, B. E., Funke, U., Mooijer, M. P. J., Langermans, J. A. M., Verschoor, E. J., Windhorst, A. D., & Stammes, M. A. (2022). Novel application of [18F]DPA714 for visualizing the pulmonary inflammation process of SARS-CoV-2-infection in rhesus monkeys (Macaca mulatta). Nuclear Medicine and Biology, 112-113, 1-8. https://doi.org/10.1016/j.nucmedbio.2022.05.002

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abstract = "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.",

keywords = "TSPO, Pulmonary inflammation, PET-CT, COVID-19, Nonhuman primates",

author = "Lisette Meijer and B{\"o}sz{\"o}rm{\'e}nyi, \{Kinga P\} and Jaco Bakker and Gerrit Koopman and Petra Mooij and Dagmar Verel and Zahra Fagrouch and Verstrepen, \{Babs E\} and Uta Funke and Mooijer, \{Martien P J\} and J.A.M. Langermans and Verschoor, \{Ernst J\} and Windhorst, \{Albert D\} and Stammes, \{Marieke A\}",

note = "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 Sk{\l}odowska-Curie Innovative Training Network HONOURs ; grant agreement no. 721367 . Publisher Copyright: {\textcopyright} 2022 The Authors",

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doi = "10.1016/j.nucmedbio.2022.05.002",

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Meijer, L, Böszörményi, KP, Bakker, J, Koopman, G, Mooij, P, Verel, D, Fagrouch, Z, Verstrepen, BE, Funke, U, Mooijer, MPJ, Langermans, JAM, Verschoor, EJ, Windhorst, AD & Stammes, MA 2022, 'Novel application of [18F]DPA714 for visualizing the pulmonary inflammation process of SARS-CoV-2-infection in rhesus monkeys (Macaca mulatta)', Nuclear Medicine and Biology, vol. 112-113, pp. 1-8. https://doi.org/10.1016/j.nucmedbio.2022.05.002

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 - https://www.scopus.com/pages/publications/85131575553

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 -

Novel application of [18F]DPA714 for visualizing the pulmonary inflammation process of SARS-CoV-2-infection in rhesus monkeys (Macaca mulatta)

Abstract

Bibliographical note

Keywords

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