TY - JOUR

T1 - Development and evaluation of an 18F-labeled nanobody to target SARS-CoV-2's spike protein

AU - Lopes van den Broek, Sara

AU - García-Vázquez, Rocío

AU - Andersen, Ida Vang

AU - Valenzuela-Nieto, Guillermo

AU - Shalgunov, Vladimir

AU - Battisti, Umberto M.

AU - Schwefel, David

AU - Modhiran, Naphak

AU - Kramer, Vasko

AU - Cheuquemilla, Yorka

AU - Jara, Ronald

AU - Salinas-Varas, Constanza

AU - Amarilla, Alberto A.

AU - Watterson, Daniel

AU - Rojas-Fernandez, Alejandro

AU - Herth, Matthias M.

N1 - Funding Information: This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 813528. Additionally, this project has received funding from the European Union's EU Framework Programme for Research and Innovation Horizon 2020, under grant agreement no. 668532. The Lundbeck Foundation (grant no. R303-2018-3567) and the Research Council for Independent Research (grant agreement no. 8022-00187B) are further acknowledged. DS was supported by the German Research Foundation (DFG) Emmy Noether Programme (SCHW1851/1-1) and by an EMBO Advanced grant (aALTF-1650). The Chilean platform for the generation and characterization of Camelid Nanobodies to A.R.F is funded by FONDECYT No. 1200427; the regional Council of the “Los Rios region” projects FICR19–20, FICR21–01; FICR20–49 to R.J; the Bio & Medical Technology Development Program of the National Research Foundation (NRF) of the Korean government (MSIT) (NRF-2020M3A9H5112395); the ANID-MPG MPG190011 and ANID-STINT CS2018–7952 grants. Publisher 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.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - alpaca

KW - biodistribution

KW - COVID-19

KW - nanobodies

KW - PET

KW - SARS-CoV-2

KW - tetrazine ligation

U2 - 10.3389/fnume.2022.1033697

DO - 10.3389/fnume.2022.1033697

M3 - Journal article

AN - SCOPUS:85183642532

VL - 2

JO - Frontiers in Nuclear Medicine

JF - Frontiers in Nuclear Medicine

SN - 2673-8880

M1 - 1033697

ER -