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Article

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

1
Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, 03-195 Warsaw, Poland
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Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland
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Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Medical University, 1 Muszynskiego St., 90-151 Lodz, Poland
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Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warszawa, Poland
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Department of Radiobiology and Radiation Protection, Military Institute of Hygiene and Epidemiology, 4 Kozielska St., 01-163 Warsaw, Poland
*
Authors to whom correspondence should be addressed.
Academic Editor: Ludmilla A. Morozova-Roche
Int. J. Mol. Sci. 2022, 23(15), 8405; https://doi.org/10.3390/ijms23158405
Received: 14 June 2022 / Revised: 20 July 2022 / Accepted: 27 July 2022 / Published: 29 July 2022
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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. View Full-Text
Keywords: tacrine; COVID-19; gallium-68; radiopharmaceuticals; biodistribution studies; molecular docking tacrine; COVID-19; gallium-68; radiopharmaceuticals; biodistribution studies; molecular docking
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MDPI and ACS Style

Koźmiński, P.; Niedziałek, D.; Wieczorek, G.; Halik, P.K.; Czarnecka, K.; Rogut, A.; Cheda, Ł.; Rogulski, Z.; Szymański, P.; Gniazdowska, E. New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer’s Disease Research. Int. J. Mol. Sci. 2022, 23, 8405. https://doi.org/10.3390/ijms23158405

AMA Style

Koźmiński P, Niedziałek D, Wieczorek G, Halik PK, Czarnecka K, Rogut A, Cheda Ł, Rogulski Z, Szymański P, Gniazdowska E. New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer’s Disease Research. International Journal of Molecular Sciences. 2022; 23(15):8405. https://doi.org/10.3390/ijms23158405

Chicago/Turabian Style

Koźmiński, Przemysław, Dorota Niedziałek, Grzegorz Wieczorek, Paweł K. Halik, Kamila Czarnecka, Aleksandra Rogut, Łukasz Cheda, Zbigniew Rogulski, Paweł Szymański, and Ewa Gniazdowska. 2022. "New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer’s Disease Research" International Journal of Molecular Sciences 23, no. 15: 8405. https://doi.org/10.3390/ijms23158405

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