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.

Application of 82 Sr/82 Rb generator in neurooncology.

INTRODUCTION: The applicability of "Rubidium Chloride, 82 Rb from Generator" radiopharmaceutical for brain tumors (BT) diagnostics is demonstrated on the basis of the application experience of the radiopharmaceutical in neurooncology. EXPERIMENTAL: A total of 21 patients with various brain tumors and nonneoplastic abnormal brain masses were investigated. RESULTS AND DISCUSSIONS: The results of the imaging and differential diagnostics of malignant and benign tumors, nonneoplastic abnormal brain masses and lesions revealed the prevalence of high uptake of the radiopharmaceutical in the malignant tumors in comparison with benign glioma and arteriovenous malformations in which 82 Rb-chloride accumulates in the vascular phase but does not linger further. The ultra-short half-life of radionuclide 82 Rb (76 s) along with a low absorbed radiation dose with 82 Rb-chloride by intravenous administration create a new possibility of successive use of two or more radiopharmaceuticals for the examination of the same patient. For instance, PET examination with 18 F-FDG, 11 C-methionine, 11 C-choline, or any other radiopharmaceutical can be carried out in just 7-15 min. after 82 Rb-chloride injection. CONCLUSION: Research demonstrated an effectiveness of 82 Rb-chloride application as a diagnostic agent in neurooncology. A method of dosing and administration of the generator-produced radiopharmaceutical has been worked out. It is possible to do up to 600 PET sessions using one Russian 82 Rb generator GR-01. The generator is proved to be reliable and easy to use. The interest in 82 Rb-chloride as a tumor-seeking radiopharmaceutical rose due to the active application of the modern devices PET/CT in the routine clinical practice.