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Synthetic Approach to 99mTc-labeled SPECT Radiotracers with Multi-nitroimidazoles for Hypoxia

  • Anh Thu Nguyen (Deparment of Nuclear Medicine, Jeonbuk National University) ;
  • Hee-Kwon Kim (Deparment of Nuclear Medicine, Jeonbuk National University)
  • Received : 2024.03.22
  • Accepted : 2024.04.23
  • Published : 2024.05.30

Abstract

Hypoxia, defined as the deficiency of oxygen, is a significant hallmark of cancers presenting in the majority of solid tumors. Detection of tumor hypoxia is essential in cancer diagnosis to prevent cancer progression, metastasis, and resistance to cancer therapies in clinical practices. Single-photon emission computed tomography (SPECT) is one of the methods studied and applied for hypoxia detection with the use of radiolabeled imaging agents in which 99mTc is the common radioisotope used for radiolabeling. Nitroimidazoles are the hypoxia-targeting moieties presenting in numerous 99mTc-radiolabeled imaging agents due to their bio-reducible ability in hypoxic environments. Recently, in addition to 99mTc-labeled radiopharmaceuticals containing one nitroimidazole unit, there has been considerable attention given to 99mTc-radiopharmaceuticals bearing two or more nitroimidazole units. This review summarizes the synthesis of hypoxia-targeting chelators and radiolabeling processes to produce these 99mTc-radiopharmaceuticals for SPECT imaging.

Keywords

References

  1. Massoud TF, Gambhir SS. Integrating noninvasive molecular imaging into molecular medicine: an evolving paradigm. Trends Mol Med. 2007;13(5):183-91. https://doi.org/10.1016/j.molmed.2007.03.003
  2. Pysz MA, Gambhir SS, Willmann JK. Molecular imaging: current status and emerging strategies. Clin Radiol. 2010;65(7):500-16. https://doi.org/10.1016/j.crad.2010.03.011
  3. Son H, Jang K, Lee H, Kim SE, Kang KW, Lee H. Use of molecular imaging in clinical drug development: a systematic review. Nucl Med Mol Imaging. 2019;53(3):208-15. https://doi.org/10.1007/s13139-019-00593-y
  4. Galban CJ, Galban S, Van Dort ME, Luker GD, Bhojani MS, Rehemtulla A, Ross BD. Applications of molecular imaging. Prog Mol Biol Transl Sci. 2010;95:237-98. https://doi.org/10.1016/B978-0-12-385071-3.00009-5
  5. Willmann JK, Van Bruggen N, Dinkelborg LM, Gambhir SS. Molecular imaging in drug development. Nat Rev Drug Discov. 2008;7(7):591-607. https://doi.org/10.1038/nrd2290
  6. Saraste A, Nekolla SG, Schwaiger M. Cardiovascular molecular imaging: an overview. Cardiovasc Res. 2009;83(4):643-52. https://doi.org/10.1093/cvr/cvp209
  7. Strafella AP, Bohnen NI, Perlmutter JS, Eidelberg D, Pavese N, Van Eimeren T, et al. Molecular imaging to track Parkinson's disease and atypical parkinsonisms: new imaging frontiers. Mov Disord. 2017;32(2):181-92. https://doi.org/10.1002/mds.26907
  8. Weissleder R. Molecular imaging in cancer. Science. 2006;312(5777):1168-71. https://doi.org/10.1126/science.1125949
  9. Emami Nejad A, Najafgholian S, Rostami A, Sistani A, Shojaeifar S, Esparvarinha M, et al. The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment. Cancer Cell Int. 2021;21(1):1-26. https://doi.org/10.1186/s12935-020-01646-5
  10. Hayashi Y, Yokota A, Harada H, Huang G. Hypoxia/pseudohypoxia-mediated activation of hypoxia-inducible factor-1α in cancer. Cancer sci. 2019;110(5):1510-7. https://doi.org/10.1111/cas.13990
  11. Crisan G, Moldovean-Cioroianu NS, Timaru DG, Andries G, Cainap C, Chis V. Radiopharmaceuticals for PET and SPECT imaging: A literature review over the last decade. Int J Mol Sci. 2022;23(9):5023.
  12. Li Y, Zhao L, Li XF. Hypoxia and the Tumor Microenvironment. Technol Cancer Res Treat. 2021;20:15330338211036304.
  13. Farina AR, Cappabianca L, Sebastiano M, Zelli V, Guadagni S, Mackay AR. Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer. J Exp Clin Cancer Res. 2020;39:1-30. https://doi.org/10.1186/s13046-019-1487-2
  14. Godet I, Doctorman S, Wu F, Gilkes DM. Detection of hypoxia in cancer models: significance, challenges, and advances. Cells. 2022;11(4):686.
  15. Walsh JC, Lebedev A, Aten E, Madsen K, Marciano L, Kolb HC. The clinical importance of assessing tumor hypoxia: relationship of tumor hypoxia to prognosis and therapeutic opportunities. Antioxid Redox Signal. 2014;21(10):1516-54. https://doi.org/10.1089/ars.2013.5378
  16. Mittal S, Mallia MB. Molecular imaging of tumor hypoxia: evolution of nitroimidazole radiopharmaceuticals and insights for future development. Bioorg Chem. 2023;20:106687.
  17. Papagiannopoulou D. Technetium-99m radiochemistry for pharmaceutical applications. J Label Compd Radiopharm. 2017;60(11):502-20. https://doi.org/10.1002/jlcr.3531
  18. Li Z, Zhang J, Jin Z, Zhang W, Zhang Y. Synthesis and biodistribution of novel 99mTc labeled 4-nitroimidazole dithiocarbamate complexes as potential agents to target tumor hypoxia. MedChemComm. 2015;6(6):1143-8. https://doi.org/10.1039/C5MD00042D
  19. Lin X, Ruan Q, Zhang X, Duan X, Teng Y, Zhang J. 99mTc labelled complexes with secnidazole xanthate: Synthesis and evaluation as potential radiotracers to target tumor hypoxia. Appl Radiat Isot. 2018;140:289-93. https://doi.org/10.1016/j.apradiso.2018.07.036
  20. Ruan Q, Zhang X, Gan Q, Zhang J. Synthesis and evaluation of [99mTcN]2+ core and [99mTcO]3+ core labeled complexes with 4-nitroimidazole xanthate derivative for tumor hypoxia imaging. Bioorg Med Chem Lett. 2020;30(22):127582.
  21. Vats K, Mallia MB, Mathur A, Sarma HD, Banerjee S. Synthesis and evaluation of a novel 99mTcN(PNP)-complex with metronidazole isocyanide ligand as a marker for tumor hypoxia. J Radioanal Nucl Chem. 2016;308:363-9. https://doi.org/10.1007/s10967-015-4526-2
  22. Mallia MB, Mathur A, Sharma R, Kumar C, Sarma HD, Banerjee S, Dash A. Preparation and preliminary evaluation of a tris-metronidazole-99mTc(CO)3 complex for targeting tumor hypoxia. J Radioanal Nucl Chem. 2018;317:1203-10. https://doi.org/10.1007/s10967-018-6012-0
  23. Ruan Q, Gan Q, Zhang X, Fang SA, Zhang J. Preparation and Bioevaluation of Novel 99mTc-Labeled Complexes with a 2-Nitroimidazole HYNIC Derivative for Imaging Tumor Hypoxia. Pharmaceuticals. 2021;14(2):158.
  24. Ruan Q, Zhang X, Zhang J. Radiosynthesis and evaluation of novel [99mTc(I)]+ and [99mTc(I)(CO)3]+ complexes with a 4-nitroimidazole isocyanide for imaging tumor hypoxia. Appl Organomet Chem. 2020;34(9):e5798.
  25. Ruan Q, Zhang X, Lin X, Duan X, Zhang J. Novel 99mTc labelled complexes with 2-nitroimidazole isocyanide: design, synthesis and evaluation as potential tumor hypoxia imaging agents. MedChemComm. 2018;9(6):988-94. https://doi.org/10.1039/C8MD00146D