In SILICO Characterization of Technetium-99M Radiotracers: ADMET Properties and Protein Interaction Profiles

  • V. Trusova Department of Medical Physics and Biomedical Nanotechnologies, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine https://orcid.org/0000-0002-7087-071X
  • U. Malovytsia Department of Medical Physics and Biomedical Nanotechnologies, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine https://orcid.org/0000-0002-7677-0779
  • P. Kuznietsov O.I. Akhiezer Department for Nuclear Physics and High Energy Physics, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine https://orcid.org/0000-0001-8477-1395
  • I. Yakymenko O.I. Akhiezer Department for Nuclear Physics and High Energy Physics, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine https://orcid.org/0000-0001-8477-1395
  • G. Gorbenko Department of Medical Physics and Biomedical Nanotechnologies, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine https://orcid.org/0000-0002-0954-5053
DOI: https://doi.org/10.26565/2312-4334-2025-2-49
Keywords: Technetium-based radiotracers, Human serum albumin, Lysozyme, Insulin, Molecular docking, SPECT imaging

Abstract

The rational design of technetium-99m (99mTc)-based radiopharmaceuticals requires a nuanced understanding of how physicochemical properties influence in vivo behavior and molecular interactions. In this study, we employed an integrated in silico framework to characterize ten clinically relevant 99mTc-labeled tracers using ADMET prediction, molecular docking with functional proteins (albumin, insulin, lysozyme), and multivariate statistical analysis. The results revealed that polarity, hydrogen bonding capacity, and molecular flexibility critically govern both pharmacokinetic properties and protein-binding profiles. Tracers such as TcSES and TcTET, with low topological polar surface area and minimal binding affinity, were associated with rapid clearance and are well suited for dynamic imaging protocols. In contrast, compounds like TcDTPA and TcDIS demonstrated strong albumin interaction and metabolic stability, supporting their use in delayed-phase imaging. TcHYN emerged as a unique tracer, exhibiting extreme polarity and promiscuous high-affinity binding across multiple protein targets. Principal component analysis and hierarchical clustering grouped tracers into functionally distinct categories, highlighting structure-dependent design trends. Collectively, these findings suggest that combined ADMET-docking profiling offers a scalable strategy for preclinical evaluation and supports the development of safer, more targeted 99mTc-based radiopharmaceuticals.

Downloads

Download data is not yet available.

References

N. Ahmed, and M. Zia, “Diagnostic modalities and radiopharmaceuticals with particular importance of technetium-99m (99mTc),” Chin. J. Acad. Radiol. 6, 143 (2023). https://doi.org/10.1007/s42058-023-00128-7

Y. Arano, “Recent advances in 99mTc radiopharmaceuticals,” Ann. Nucl. Med. 16, 79 (2002). https://doi.org/10.1007/BF02993710

G. Xiong, Z. Wu, and J. Yi, “ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties,” Nucleic Acids Res. 49, W5 (2021). https://doi.org/10.1093/nar/gkab255

Y. Yan, H. Tao, J. He, and S. Huang, “The HDOCK server for integrated protein–protein docking,” Nature Protocols, 15, 1829 (2020). https://doi.org/10.1038/s41596-020-0312-x

A. Alkandari, Y. Alsayed, and A. El-Hanbaly, “Enhanced efficacy of radiopharmaceuticals when using technetium-99m-labeled liposomal agents: synthesis and pharmacokinetic properties,” Biomedicines, 10, 2994 (2022). https://doi.org/10.3390/biomedicines10112994

S. Rathmann, Z. Ahmad, S. Slikboer, H. Bilton, D. Snider, and J. Valliant, “The radiopharmaceutical chemistry of technetium-99m,” in: Radiopharmaceutical Chemistry, edited by J. Lewis, A. Windhorst, and B. Zeglis, (Springer, Cham., 2019). http://dx.doi.org/10.1007/978-3-319-98947-1_18

B. Lee, J. Yeh, N. Chiu, G. Liu, H. Yu, M. Wang, and L. Shen, “Evaluation of Tc-99m (V) DMSA binding to human plasma proteins,” Kaohsiung J. Med. Sci. 24, 1 (2008). http://dx.doi.org/10.1016/S1607-551X(08)70066-4

L. Shattuck, D. Eshima, A. Taylor, et al., “Evaluation of the hepatobiliary excretion of technetium-99m-MAG3 and reconstitution factors affecting radiochemical purity,” J. Nucl. Med. 35, 349 (1994). https://doi.org/10.29011/2577-2201.100088

A. Mori, Y. Saito, and K. Nakamura, “Microcalcification and 99mTc-pyrophosphate uptake without increased bone metabolism in cardiac tissue from patients with transthyretin cardiac amyloidosis,” Int. J. Mol. Sci. 24, 1921 (2023). https://doi.org/10.3390/ijms24031921

J. Smith, and J. Pfaendtner, “Elucidating the molecular interactions between uremic toxins and the Sudlow II binding site of human serum albumin,” J. Phys. Chem. B, 14, 3922 (2020). https://doi.org/10.1021/acs.jpcb.0c02015

Published
2025-06-09
Cited
How to Cite
Trusova, V., Malovytsia, U., Kuznietsov, P., Yakymenko, I., & Gorbenko, G. (2025). In SILICO Characterization of Technetium-99M Radiotracers: ADMET Properties and Protein Interaction Profiles. East European Journal of Physics, (2), 405-411. https://doi.org/10.26565/2312-4334-2025-2-49
Issue
No. 2 (2025): East European Journal of Physics
Section
Original Papers

Copyright (c) 2025 V. Trusova, U. Malovytsia, P. Kuznietsov, I. Yakymenko, G. Gorbenko

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with this journal agree to the following terms:

    • Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
    • Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
    • Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).

Most read articles by the same author(s)

<< < 1 2