New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer’s Disease Research

Viral pneumonia caused by highly infectious SARS-CoV-2 poses a higher risk to older people and those who have underlying health conditions, including Alzheimer’s disease. In this work we present newly designed tacrine-based radioconjugates with physicochemical and biological properties that are cruc...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-07, Vol.23 (15), p.8405
Main Authors: Koźmiński, Przemysław, Niedziałek, Dorota, Wieczorek, Grzegorz, Halik, Paweł K., Czarnecka, Kamila, Rogut, Aleksandra, Cheda, Łukasz, Rogulski, Zbigniew, Szymański, Paweł, Gniazdowska, Ewa
Format: Article
Language:English
Subjects:
Acetylcholinesterase
Affinity
Alzheimer's disease
Biodistribution
biodistribution studies
Biological properties
Biomarkers
Coronaviruses
COVID-19
Dementia
Gallium
gallium-68
Ligands
Lungs
Medical imaging
molecular docking
Molecular modelling
Neurodegeneration
Pharmaceuticals
Physicochemical properties
Physiology
Pneumonia
Positron emission
Radiochemistry
Radioisotopes
radiopharmaceuticals
Severe acute respiratory syndrome coronavirus 2
Tacrine
Tomography
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Summary:Viral pneumonia caused by highly infectious SARS-CoV-2 poses a higher risk to older people and those who have underlying health conditions, including Alzheimer’s disease. In this work we present newly designed tacrine-based radioconjugates with physicochemical and biological properties that are crucial for the potential application as diagnostic radiopharmaceuticals. A set of ten tacrine derivatives was synthesized, labelled with gallium-68 and fully characterized in the context of their physicochemical properties. Based on these results, the final two most promising radioconjugates, [68Ga]Ga-NODAGA-Bn-NH(CH2)9Tac and [68Ga]Ga-THP-NH(CH2)9Tac, were selected for biodistribution studies. The latter compound was proven to be a good inhibitor of cholinesterases with significant affinity toward the lungs, according to the biodistribution studies. On the basis of molecular modelling combined with in vitro studies, we unraveled which structural properties of the developed tacrine derivatives are crucial for high affinity toward acetylcholinesterase, whose increased levels in lung tissues in the course of coronavirus disease indicate the onset of pneumonia. The radiopharmaceutical [68Ga]Ga-THP-NH(CH2)9Tac was ultimately selected due to its increased accuracy and improved sensitivity in PET imaging of lung tissue with high levels of acetylcholinesterase, and it may become a novel potential diagnostic modality for the determination of lung perfusion, including in inflammation after COVID-19.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23158405