Development and evaluation of an 18F-labeled nanobody to target SARS-CoV-2's spike protein

COVID-19, caused by the SARS-CoV-2 virus, has become a global pandemic that is still present after more than two years. COVID-19 is mainly known as a respiratory disease that can cause long-term consequences referred to as long COVID. Molecular imaging of SARS-CoV-2 in COVID-19 patients would be a p...

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Published inFrontiers in nuclear medicine Vol. 2; p. 1033697
Main Authors Lopes van den Broek, Sara, García-Vázquez, Rocío, Andersen, Ida Vang, Valenzuela-Nieto, Guillermo, Shalgunov, Vladimir, Battisti, Umberto M., Schwefel, David, Modhiran, Naphak, Kramer, Vasko, Cheuquemilla, Yorka, Jara, Ronald, Salinas-Varas, Constanza, Amarilla, Alberto A., Watterson, Daniel, Rojas-Fernandez, Alejandro, Herth, Matthias M.
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 23.11.2022
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Nuclear Medicine
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Abstract COVID-19, caused by the SARS-CoV-2 virus, has become a global pandemic that is still present after more than two years. COVID-19 is mainly known as a respiratory disease that can cause long-term consequences referred to as long COVID. Molecular imaging of SARS-CoV-2 in COVID-19 patients would be a powerful tool for studying the pathological mechanisms and viral load in different organs, providing insights into the disease and the origin of long-term consequences and assessing the effectiveness of potential COVID-19 treatments. Current diagnostic methods used in the clinic do not allow direct imaging of SARS-CoV-2. In this work, a nanobody (NB) – a small, engineered protein derived from alpacas – and an Fc-fused NB which selectively target the SARS-CoV-2 Spike protein were developed as imaging agents for positron emission tomography (PET). We used the tetrazine ligation to 18 F-label the NB under mild conditions once the NBs were successfully modified with trans- cyclooctenes (TCOs). We confirmed binding to the Spike protein by SDS-PAGE. Dynamic PET scans in rats showed excretion through the liver for both constructs. Future work will evaluate in vivo binding to the Spike protein with our radioligands.
AbstractList COVID-19, caused by the SARS-CoV-2 virus, has become a global pandemic that is still present after more than two years. COVID-19 is mainly known as a respiratory disease that can cause long-term consequences referred to as long COVID. Molecular imaging of SARS-CoV-2 in COVID-19 patients would be a powerful tool for studying the pathological mechanisms and viral load in different organs, providing insights into the disease and the origin of long-term consequences and assessing the effectiveness of potential COVID-19 treatments. Current diagnostic methods used in the clinic do not allow direct imaging of SARS-CoV-2. In this work, a nanobody (NB) - a small, engineered protein derived from alpacas - and an Fc-fused NB which selectively target the SARS-CoV-2 Spike protein were developed as imaging agents for positron emission tomography (PET). We used the tetrazine ligation to 18F-label the NB under mild conditions once the NBs were successfully modified with trans-cyclooctenes (TCOs). We confirmed binding to the Spike protein by SDS-PAGE. Dynamic PET scans in rats showed excretion through the liver for both constructs. Future work will evaluate in vivo binding to the Spike protein with our radioligands.COVID-19, caused by the SARS-CoV-2 virus, has become a global pandemic that is still present after more than two years. COVID-19 is mainly known as a respiratory disease that can cause long-term consequences referred to as long COVID. Molecular imaging of SARS-CoV-2 in COVID-19 patients would be a powerful tool for studying the pathological mechanisms and viral load in different organs, providing insights into the disease and the origin of long-term consequences and assessing the effectiveness of potential COVID-19 treatments. Current diagnostic methods used in the clinic do not allow direct imaging of SARS-CoV-2. In this work, a nanobody (NB) - a small, engineered protein derived from alpacas - and an Fc-fused NB which selectively target the SARS-CoV-2 Spike protein were developed as imaging agents for positron emission tomography (PET). We used the tetrazine ligation to 18F-label the NB under mild conditions once the NBs were successfully modified with trans-cyclooctenes (TCOs). We confirmed binding to the Spike protein by SDS-PAGE. Dynamic PET scans in rats showed excretion through the liver for both constructs. Future work will evaluate in vivo binding to the Spike protein with our radioligands.
COVID-19, caused by the SARS-CoV-2 virus, has become a global pandemic that is still present after more than two years. COVID-19 is mainly known as a respiratory disease that can cause long-term consequences referred to as long COVID. Molecular imaging of SARS-CoV-2 in COVID-19 patients would be a powerful tool for studying the pathological mechanisms and viral load in different organs, providing insights into the disease and the origin of long-term consequences and assessing the effectiveness of potential COVID-19 treatments. Current diagnostic methods used in the clinic do not allow direct imaging of SARS-CoV-2. In this work, a nanobody (NB) – a small, engineered protein derived from alpacas – and an Fc-fused NB which selectively target the SARS-CoV-2 Spike protein were developed as imaging agents for positron emission tomography (PET). We used the tetrazine ligation to 18 F-label the NB under mild conditions once the NBs were successfully modified with trans- cyclooctenes (TCOs). We confirmed binding to the Spike protein by SDS-PAGE. Dynamic PET scans in rats showed excretion through the liver for both constructs. Future work will evaluate in vivo binding to the Spike protein with our radioligands.
Author Amarilla, Alberto A.
Rojas-Fernandez, Alejandro
Battisti, Umberto M.
Salinas-Varas, Constanza
Watterson, Daniel
Kramer, Vasko
Cheuquemilla, Yorka
Lopes van den Broek, Sara
Herth, Matthias M.
Schwefel, David
Modhiran, Naphak
García-Vázquez, Rocío
Shalgunov, Vladimir
Andersen, Ida Vang
Valenzuela-Nieto, Guillermo
Jara, Ronald
AuthorAffiliation 8 Department of Clinical Physiology, Nuclear Medicine & PET , Rigshospitalet Copenhagen University Hospital , Copenhagen , Denmark
5 Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia , QLD , Australia
2 Institute of Medicine, Faculty of Medicine & Center for Interdisciplinary Studies on the Nervous System, CISNE , Universidad Austral de Chile , Valdivia , Chile
1 Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark
6 Positronpharma SA , Providencia, Santiago , Chile
4 School of Chemistry and Molecular Biosciences , University of Queensland, St Lucia , QLD , Australia
7 Berking Biotechnology , Valdivia , Chile
3 Institute of Medical Physics and Biophysics , Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin , Berlin , Germany
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– name: 8 Department of Clinical Physiology, Nuclear Medicine & PET , Rigshospitalet Copenhagen University Hospital , Copenhagen , Denmark
– name: 2 Institute of Medicine, Faculty of Medicine & Center for Interdisciplinary Studies on the Nervous System, CISNE , Universidad Austral de Chile , Valdivia , Chile
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Copyright 2022 Lopes van den Broek, García-Vázquez, Andersen, Valenzuela-Nieto, Shalgunov, Battisti, Schwefel, Modhiran, Kramer, Cheuquemilla, Jara, Salinas-Varas, Amarilla, Watterson, Rojas-Fernandez and Herth.
2022 Lopes van den Broek, García-Vázquez, Andersen, Valenzuela-Nieto, Shalgunov, Battisti, Schwefel, Modhiran, Kramer, Cheuquemilla, Jara, Salinas-Varas, Amarilla, Watterson, Rojas-Fernandez and Herth. 2022 Lopes van den Broek, García-Vázquez, Andersen, Valenzuela-Nieto, Shalgunov, Battisti, Schwefel, Modhiran, Kramer, Cheuquemilla, Jara, Salinas-Varas, Amarilla, Watterson, Rojas-Fernandez and Herth
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– notice: 2022 Lopes van den Broek, García-Vázquez, Andersen, Valenzuela-Nieto, Shalgunov, Battisti, Schwefel, Modhiran, Kramer, Cheuquemilla, Jara, Salinas-Varas, Amarilla, Watterson, Rojas-Fernandez and Herth. 2022 Lopes van den Broek, García-Vázquez, Andersen, Valenzuela-Nieto, Shalgunov, Battisti, Schwefel, Modhiran, Kramer, Cheuquemilla, Jara, Salinas-Varas, Amarilla, Watterson, Rojas-Fernandez and Herth
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Reviewed by: Sridhar Goud Nerella, National Institutes of Health (NIH), United States Laurence Carroll, Johns Hopkins University, United States Weijun Wei, Shanghai Jiao Tong University, China
Edited by: Oliver Kiß, Institute for Radiopharmaceutical Cancer Research, Germany
Specialty Section: This article was submitted to Radiopharmacy and Radiochemistry, a section of the journal Frontiers in Nuclear Medicine
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Snippet COVID-19, caused by the SARS-CoV-2 virus, has become a global pandemic that is still present after more than two years. COVID-19 is mainly known as a...
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StartPage 1033697
SubjectTerms Nuclear Medicine
Title Development and evaluation of an 18F-labeled nanobody to target SARS-CoV-2's spike protein
URI https://www.proquest.com/docview/3112116885
https://pubmed.ncbi.nlm.nih.gov/PMC11440877
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