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

• Published in: Frontiers 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
• Language: English
• Published: Switzerland 2022
• Subjects: COVID-19; SARS-CoV-2; biodistribution; nanobodies; alpaca; tetrazine ligation; PET

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 F-label the NB under mild conditions once the NBs were successfully modified with 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 binding to the Spike protein with our radioligands.