Interactions Between Technetium-99m Radiopharmaceuticals and Plasma Proteins: A Molecular Docking Study
Abstract
Technetium-99m (99mTc) is the most widespread radionuclide with physicochemical characteristics highly suitable for diagnostic nuclear medicine. The radiopharmaceuticals obtained by complexation of 99mTc with ligating agents or targeting biomolecules are increasingly used for diagnostic purposes in oncology, cardiology, nephrology, neurology and other fields of medical practice. One factor that may influence clinical efficiency of 99mTc radiotracers involves their interactions with the proteins of human blood plasma. Most studies of such kind of interactions have been focused on albumin, while much less attention was given to other protein components of blood plasma. In the present work the molecular docking technique was employed to evaluate the possibility of association between a series of 99mTc radiopharmaceuticals and plasma proteins including transthyretin, fibrinogen, alpha1-acid glycoprotein, Fc and Fab fragments of immunoglobulin G. It was found that the investigated 99mTc compounds (except pertechnetate) form the strongest complexes with alpha1-acid glycoprotein and fibrinogen. The affinities of TcMED, TcDTPA, TcMAG, TcECD, TcDIS and TcMEB for alpha1-acid glycoprotein and fibrinogen appeared to be higher than those for albumin. The structural characteristics of both plasma proteins and 99mTc radiotracers were demonstrated to determine the amino acid composition of the binding sites. The presence of peptide fragments in the structure of 99mTc compounds was assumed to markedly increase their affinity for plasma proteins. The results obtained may be helpful for gaining deeper insights into biodistribution pattern of 99mTc radiopharmaceuticals.
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M.U. Akbar, M.R. Ahmad, A. Shaheen, and S. Mushtaq, J. Radioanal. Nucl. Chem. 310, 477–493 (2016). https://doi.org/10.1007/s10967-016-5019-7
T. J. Ruth, Annu. Rev. Nucl. Part. Sci. 70, 77–94 (2020). https://doi.org/10.1146/annurev-nucl-032020-021829
M. T. Ma, Front. Chem. Biol. 4, 1729615 (2026). https://doi.org/10.3389/fchbi.2025.1729615
G. M. Currie, and E. M. Rohren, Semin. Nucl. Med. 55, 829-840 (2025). https://doi.org/10.1053/j.semnuclmed.2025.01.005
E. Strub, D. Badea, J. Bruns, A. Frontera, N. Mayordomo, A. Sakhonenkova, M. R. Jungfer, M. Wickleder, C.Yong, and M. Zegke, Eur. J. Inorg. Chem. 28, e202400780 (2025). https://doi.org/10.1002/ejic.202400780
N. Ahmed, and M. Zia, J. Acad. Radiol. 6, 143–159 (2023). https://doi.org/10.1007/s42058-023-00128-7
A. Maruk, A. Bruskin, and G. Kodina, Radiochemistry 53, 341–353 (2011). https://doi.org/10.1134/S1066362211040011
I. Ibrahim, J. Radioanal. Nucl. Chem, 281, 669–674 (2009). https://doi.org/10.1007/s10967-009-0040-8
M. Sanad, Radiochemistry 55, 539–544 (2013). https://doi.org/10.1134/S1066362213050159
E. von Guggenberg, H. Dietrich, I. Skvortsova, M. Gabriel, I. Virgolini, and C. Decristoforo, Eur. J. Nucl. Med. Mol. Imaging 34, 1209–1218 (2007). https://doi.org/10.1007/s00259-006-0348-3
Y. Arano, Ann. Nucl. Med. 16, 79–93 (2002). https://doi.org/10.1007/BF02993710
A. S. Dzik-Jurasz, Br. J. Radiol. 76, 98–109 (2003). https://doi.org/10.1259/bjr/25833499
V. Trusova, U. Malovytsia, P. Kuznietsov, I. Yakymenko, and G. Gorbenko, East Eur. J. Phys. 2, 405-411 (2025). https://doi.org/10.26565/2312-4334-2025-2-49
M. A. Liz, T. Coelho, V. Bellotti M. I. Fernandez-Arias, P. Mallaina, and L. Obici, Neurol. Ther. 9, 395–402 (2020). https://doi.org/10.1007/s40120-020-00217-0
A. S. Wolberg, J. Thromb. Haemost. 21, 3005-3015 (2023). https://doi.org/10.1016/j.jtha.2023.08.014
T. Fournier, N. Medjoubi, and D. Porquet, Biochim. Biophys. Acta Protein Struct. Mol. Enzymol. 1482, 157–171 (2000). https://doi.org/10.1016/S0167-4838(00)00153-9
S. Yanaka, R. Yogo,and K. Kato, Biophys. Rev. 12, 637–645 (2020). https://doi.org/10.1007/s12551-020-00698-1
S. Rathmann, Z. Ahmad, S. Slikboer, H. Bilton, D. Snider, and J. Valliant, In: J. Lewis, A. Windhorst, B. Zeglis (eds) Radiopharmaceutical Chemistry. Springer, Cham. (2019). https://doi.org/10.1007/978-3-319-98947-1_18
Y. Yan, H. Tao, J. He, and S-Y. Huang, Nat. Protoc. 15, 1829–1852 (2020). https://doi.org/10.1038/s41596-020-0312-x
V. Trusova, P. Kuznietsov, I. Yakymenko, and G. Gorbenko, East Eur. J. Phys. 1, 520-524 (2026). https://doi.org/10.26565/2312-4334-2026-1-59
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