N-Benzylethanolammonium Ionic Liquids and Molten Salts in the Synthesis of 68Ga- and Al18F-Labeled Radiopharmaceuticals.

Ionic liquids (ILs), due to their structural features, have unique physical and chemical properties and are environmentally friendly. Every year, the number of studies devoted to the use of ILs in medicine and pharmaceutics is growing. In nuclear medicine, the use of ILs with self-buffering capacity in the synthesis of radiopharmaceuticals is extremely important. This research is devoted to obtaining new ionic buffer agents containing N-benzylethanolammonium (BEA) cations and anions of carboxylic acids. A series of new BEA salts was synthesized and identified by NMR (1H, 13C), IR spectroscopy and elemental and thermal analysis. The crystal structures of BEA hydrogen succinate, hydrogen oxalate and oxalate were determined by x-ray diffraction. Newly synthesized compounds were tested as buffer solutions in 68Ga- and Al18F-radiolabeling reactions with a series of bifunctional chelating agents and clinically relevant peptides used for visualization of malignancies by positron emission tomography. The results obtained confirm the promise of using new buffers in the synthesis of 68Ga- and Al18F-labeled radiopharmaceuticals.

Impact of metallic coating on the retention of 225Ac and its daugthers within core-shell nanocarriers.

Currently, alpha-emitting radionuclide 225Ac is one of the most promising isotopes in alpha therapy due to its high linear energy transfer during four sequential alpha decays. However, the main obstacle preventing the full introduction of 225Ac into clinical practice is the lack of stable retention of radionuclides, leading to free circulation of toxic isotopes in the body. In this work, the surface of silica nanoparticles (SiO2 NPs) has been modified with metallic shells composed of titanium dioxide (TiO2) and gold (Au) nanostructures to improve the retention of 225Ac and its decay products within the developed nanocarriers. In vitro and in vivo studies in healthy mice show that the metallic surface coating of SiO2 NPs promotes an enhanced sequestering of radionuclides (225Ac and its daughter isotopes) compared to non-modified SiO2 NPs for a prolonged period of time. Histological analysis reveals that for the period of 3-10 d after the injections, the developed nanocarriers have no significant toxic effects in mice. At the same time, almost no accumulation of leaked radionuclides can be detected in non-target organs (e.g., in the kidneys). In contrast, non-modified carriers (SiO2 NPs) demonstrate the release of free radionuclides, which are distributed over the whole animal body with the consequent morphological changes in the lung, liver and kidney tissues. These results highlight the potential of the developed nanocarriers to be utilized as radionuclide delivery systems and offer an insight into design rules for the fabrication of new nanotherapeutic agents.

Calcium Carbonate Core-Shell Particles for Incorporation of 225Ac and Their Application in Local α-Radionuclide Therapy.

Actinium-225 (225Ac) radiolabeled submicrometric core-shell particles (SPs) made of calcium carbonate (CaCO3) coated with biocompatible polymers [tannic acid-human serum albumin (TA/HSA)] have been developed to improve the efficiency of local α-radionuclide therapy in melanoma models (B16-F10 tumor-bearing mice). The developed 225Ac-SPs possess radiochemical stability and demonstrate effective retention of 225Ac and its daughter isotopes. The SPs have been additionally labeled with zirconium-89 (89Zr) to perform the biodistribution studies using positron emission tomography-computerized tomography (PET/CT) imaging for 14 days after intratumoral injection. According to the PET/CT analysis, a significant accumulation of 89Zr-SPs in the tumor area is revealed for the whole investigation period, which correlates with the direct radiometry analysis after intratumoral administration of 225Ac-SPs. The histological analysis has revealed no abnormal changes in healthy tissue organs after treatment with 225Ac-SPs (e.g., no acute pathologic findings are detected in the liver and kidneys). At the same time, the inhibition of tumor growth has been observed as compared with control samples [nonradiolabeled SPs and phosphate-buffered saline (PBS)]. The treatment of mice with 225Ac-SPs has resulted in prolonged survival compared to the control samples. Thus, our study validates the application of 225Ac-doped core-shell submicron CaCO3 particles for local α-radionuclide therapy.