ИСТИНА

The development of novel radiopharmaceuticals for early diagnosis and treatment of socially significant diseases is extremely important for improvement the standard of living. In particular, oncological diseases can be detected and treated at an early stage by radionuclide-labeled structures with an affinity for tumor cells. Thus, registration of γ-radiation is used in modern methods of molecular imaging (such as PET and SPECT), while corpuscular α- and β-radiation (characterized by a high linear energy transfer) is used for the treatment of malignant neoplasms. Moreover, for use in medical purposes, a radionuclide must have suitable nuclear-physical properties, such as the type and energy of radiation, as well as a half-life. In particular, the characteristics of zinc isotopes Zn-62 and Zn-63 allow us to consider them for use in positron emission tomography (including in the form of in vivo generator Zn-62 / Cu-62), while alpha-emitting isotopes of bismuth Bi-212 and Bi-213 are already showing their efficacy in clinical trials of targeted alpha therapy drugs. In most cases, for targeted delivery to the area of interest or diseased tissue, the binding of a radionuclide to a biological vector is required. However, their direct conjugation most often does not lead to the formation of a stable compound. Therefore, in this case, bifunctional ligands are used that form stable complexes with the cation of the radionuclide and are simultaneously covalently bound to the vector. One of the best options for chelators are azacrown ethers with a large cavity in the macrocycle, since they effectively and quickly bind metal cations into a stable complex that does not dissociate in a living organism. A relatively new and promising direction of research in nuclear medicine for early diagnosis and effective treatment of cancer is the development of biocompatible nanomaterials labeled with radionuclides. Nanoparticles can be a convenient platform for the development of combined radiopharmaceuticals. For example, nanosized cerium dioxide has antioxidant properties, which makes it possible to use it as a radioprotector to minimize the damage of ionizing radiation of a radiopharmaceutical to healthy organs and tissues. At the same time, cerium dioxide in malignant neoplasms shows prooxidant properties due to the lower pH in this type of cells, which will potentially enhance the therapeutic effect of radiopharmaceutical. Finally, due to its pH sensitivity, cerium oxide exhibits vector properties and is able to deliver targeted radiopharmaceutical to the affected tissue. In this project, new conjugates of nanoparticles of cerium dioxide and azacrown ether L with six nitrogen atoms in a macrocycle, for which the stability of complexes with zinc and bismuth under in vivo conditions has been demonstrated. The labeled nanoparticle-ligand-radionuclide structures will be examined for their stability in biologically significant media, and data on their distribution in a living organism will also be obtained. It should be noted that cerium dioxide nanoparticles are currently extremely poorly studied from the point of view of their potential use in nuclear medicine, despite the potential interest in this material in terms of its ability to neutralize reactive oxygen species formed when the body is exposed to ionizing radiation. In this regard, the results of research within the framework of this project can become the basis for the creation of a fundamentally new class of theranostic radiopharmaceuticals.