Quantum-Chemical Calculations of Technetium Radiopharmaceuticals
Abstract
The synthesis of radiopharmaceuticals is a major task of nuclear medicine, and Technetium-99m (99mTc) has ideal nuclear properties for non-invasive nuclear medical diagnostics by single-photon emission computed tomography (SPECT) – a cheaper method than CT, MRI, and PET, suitable for developing countries. Of particular relevance today is the design of various covalently labelled 99mTc radiopharmaceuticals for the diagnosis and theranostics of oncological diseases. However, the correct selection of ligands and the development of high-quality 99mTc-based imaging agents that will not disrupt the functions of biologically active molecules requires a good understanding of the coordination chemistry of group 7 transition metals. In this work, the quantum-chemical characteristics of ten 99mTc radiopharmaceuticals were calculated using ab initio (a combined basis set: SBKJC on the Tc atom and 6-31G (d,p)/DFT – on other atoms, Gamess) and semi-empirical (PM6, MOPAC) methods. Negative (for Tc-Exametazime, Tc-ECD) and positive (for other 99mTc complexes) values of the ЕLUMO parameter indicated the electrophilic and nucleophilic properties of the radiopharmaceuticals, respectively. Analysis of the absolute hardness values of the complexes revealed that the studied radiopharmaceuticals are soft reagents, with Pertechnetate having the lowest reactivity, which is consistent with the literature data. Dipole moments of most of the 99mTc radiopharmaceuticals were similar or up to one order of magnitude greater as compared to that of a water molecule. Finally, a strong correlation was established between the ground state dipole moments, lipophilicity and the percentage of nonspecific binding of five radiopharmaceuticals (Tc-Exametazime, Tc-MAG3, Tc-MDP, Tc(III)-DMSA, Tc-DTPA) to plasma proteins (Pearson’s correlation coefficients were ca. -0.719 and 0.611, respectively). The obtained results could be employed for the design of new 99mTc-based theranostic agents suitable for cancer treatment, in particular those with high nonspecific binding to plasma proteins.
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