Vol 25, No 2 (2026)

Background. Radionuclide therapy and molecular imaging are promising areas of nuclear medicine based on the selective accumulation of radiopharmaceuticals in pathological foci. Hyaluronic acid (HA) is of particular interest as a biocompatible platform for targeted radionuclide delivery due to its binding to CD44 (cluster of differentiation 44), RHAMM (receptor for hyaluronan-mediated motility), and TRL (Toll-like receptors) overexpressed in tumor, inflammatory, and degenerative diseases.

Aim. Analysis of modern approaches for the obtaining of radiolabeled HA, radionuclides used, imaging methods and prospects for the use of hyaluronic-based matrices in the diagnosis and theranostics of diseases.

Materials and methods. The analysis of hyaluronic-based matrices data published mainly after 2020 and presented in the international scientific databases PubMed, Google Scholar, Scopus and other peer-reviewed sources is carried out. Additionally, early fundamental research on the metabolism and radiotherapy of HA is reviewed.

Results. The main methods for the obtaining of radiolabeled HA, including direct and chelator-mediated labeling, as well as the most commonly used radionuclides for diagnosis and therapy, including technetium-99m, gallium-68, iodine-125, iodine-131, lutetium-177 and yttrium-90, are considered. It has been shown that due to its high biocompatibility, the presence of functional groups for modification, and the ability to selectively bind to cellular receptors, HA provides targeted accumulation of radiopharmaceuticals in tumor, inflammatory, and fibrous tissues. Special attention is paid to the methods of single-photon emission computed tomography and positron emission tomography with computed tomography, which make it possible to visualize the bio-distribution of radiolabeled hyaluronic matrices in vivo. Examples of radiopharmaceuticals based on HA containing additional therapeutic agents, including curcumin, for the realization of a synergistic theranostic effect are considered.

Conclusion. HA is a promising platform for the creation of radiopharmaceuticals due to its high biocompatibility, the possibility of chemical modification and selective interaction with receptors of pathologically altered tissues. The use of radiolabeled hyaluronic matrices opens up broad prospects for the development of personalized diagnostics, molecular imaging, and targeted radionuclide therapy.

Background. Secondary immunodeficiency in patients with pulmonary tuberculosis has a significant impact on the course and outcome of the disease. Recombinant (rIL-2) interleukin-2 (IL-2) preparations are considered the most promising for pathogenetic immunotherapy.

Aim. Systematization of data confirming the association of secondary immune deficiency and IL-2 deficiency with the pathogenesis of pulmonary tuberculosis and evaluation of the results of using rIL-2 as a pathogenetically substantiated means of immunocorrection.

Materials and methods. Medline / PubMed, eLibrary, and CyberLeninka were used to search for scientific publications. Articles relevant to the review objective were identified for the period from 1997 to 2025 using the following terms: tuberculosis, Mycobacterium tuberculosis, and immunity.

Results. A systematic review based on a literature search for sources characterizing the state of immunoreactivity in patients with destructive pulmonary tuberculosis and the effectiveness of combined use of anti-tuberculosis chemotherapy and rIL-2 showed that secondary immune deficiency is associated with various forms of destructive pulmonary tuberculosis and manifests itself in the form of lymphopenia, cellular immune deficiency, including a quantitative deficiency of CD4⁺ and / or CD8⁺ lymphocytes, suppression of their functional activity, and production of IL-2. Twenty studies were devoted to the use of rIL-2 in combination with standard polychemotherapy for pulmonary tuberculosis, in which bacteriological, immunological, and radiological research outcomes were assessed along with clinical symptoms. All studies were randomized, 2 of which were double-blind, randomized, placebo-controlled studies. The studies included a total of 2,730 patients suffering from various forms of destructive pulmonary tuberculosis. Various doses, routes of administration of rIL-2, and durations of immune therapy were used. The use of rIL-2 in combination with anti-tuberculosis chemotherapy helps to correct secondary immunodeficiency, restore quantitative and functional immune parameters, and increase the frequency of abacillization, leading to positive radiological dynamics and improved clinical outcomes.

Conclusion. The inclusion of cytokine therapy with rIL-2 in the standard anti-tuberculosis polychemotherapy is pathogenetically justified, reliably increases the effectiveness of treatment and has a good safety profile.

Background. The significance of specific mutation variants, particularly rare ones, in patients with colorectal cancer (CRC) and isolated liver metastases is insufficiently studied, while the possibility of achieving resectability is critical in the context of prognosis and survival.

Aim. To assess the prognostic significance of various mutations in the KRAS, NRAS, and BRAF genes in patients with CRC.

Materials and methods. The study included 366 patients with CRC and isolated liver metastases. Group 1 (n = 198) included patients with mutations in KRAS, NRAS, BRAF (Mut) genes, and Group 2 (n = 168) included those without activating mutations (wild-type – wt). Progression-free survival (PFS), risk of progression, rate and chance of achieving resectability were assessed.

Results. Group 1 showed worse outcomes compared to Group 2: a lower rate of liver resection (36.9 % vs 49.4 %; p = 0.016) and a shorter median PFS (10.3 vs 12.9 months; hazard ratio 1.57 [95 % confidence interval 1.24–1.99; p < 0.001). Significant heterogeneity was revealed among Mut patients. The worst prognosis was associated with KRAS G12D mutations (median PFS 5.9 months; hazard ratio 2.99 [95 % confidence interval 2.08–4.3; p < 0.001), as well as G12C, G12A, and BRAF mutations. However, performing liver resection improves long-term outcomes even in this patient subgroup. In contrast, patients with KRAS G13D mutations and rare A146 / K117 / Q61 mutations demonstrated significantly better long-term outcomes and a high rate of resectability.

Conclusion. This study evaluates the prognostic value of RAS / BRAF mutations in patients with CRC and isolated liver involvement. These findings are essential for patient stratification in the current era of personalized therapy.

Background. Previously, the main pathogenicity factors of closely related strains of Mitis group streptococci of different virulence, including Streptococcus pneumoniae and Streptococcus oralis, were determined. Differences in the protein composition of protein-containing fractions (PCF) with a molecular weight of 30–100 kDa isolated from them using Amicon®Ultra filters (Millipore, Ireland) were established. It was of interest to obtain PCF by gel filtration (PCF-C) and the determination of the possibility of its use in the development of an antipneumococcal drug.

Aim. Comparison of the immunobiological properties of PCF from the S. oralis strain isolated by different methods and a study of the protective activity of a mixture of antigens of the Mitis group of streptococci.

Materials and methods. PCF-C was prepared by exclusion chromatography on a Toyopearl HW-55 column. Surface protein-containing antigens of S. oralis were assessed by protein content using the Lowry method and electrophoretic characteristics using the Laemmli method. The protective activity was studied in experiments on active protection of BALB / c mice with two intraperitoneal injections (with an interval of 14 days) of three preparations: PCF and PCF-C (50 μg protein / mouse) and a mixture of PCF-C + recombinant atoxic pneumolysin (raPly) (25 μg protein / mouse). Immunized mice were intranasally infected with a virulent strain of S. pneumoniae serotype 3 No. 10196. The level of specific immunoglobulin G (IgG) antibodies was determined in the hyperimmune sera of mice using solid-phase enzyme-linked immunosorbent assay. Statistical processing of the results was performed using parametric and nonparametric comparison methods.

Results. A comparative analysis of the PCF-C and PCF series established their protective activity against the virulent strain of S. pneumoniae; both preparations induced the production of specific IgG antibodies, did not differ in protein yield and were non-toxic. The protective activity of the PCF-C + raPly mixture was established.

Conclusion. The feasibility of using a surface protein-containing antigen of S. oralis obtained using size-exclusion chromatography, including as part of a two-component experimental preparation in a mixture with raPly not sorbed on aluminum hydroxide, is demonstrated.

Background. The development of innovative national antitumor drugs remains an ultimately important task. Among the new drugs, which selectively affect tumors, indolo [2,3-a] carbazole – N-glycosides LCS-1208 and LCS-1269, synthesized using an original technique at the Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, are of essential interest. The paper presents possible options of instrumental analytical methods for identification of differences in the physical chemical features of structurally similar compounds LCS-1208 and LC S-1269. These methods may be used for establishing experimentally justified standards of quality for the standardization of the compounds as pharmaceutical substances.

Aim. To study the physical chemical features and to develop methods for the qualitative and quantitative analysis of LCS-1208 and LCS-1269.

Materials and methods. The study involved modern instrumental methods of analysis, such as polarimetry, ultraviolet spectroscopy, infrared spectroscopy, proton magnetic resonance spectroscopy spectroscopy, high performance liquid chromatography (HPLC), and HPLC with the tandem mass spectrometric detection (HPLC–MS / MS).

Results. Significant differences in the physical chemical features of the original N-glycosides LCS-1208 and LCS-1269 were determined using modern instrumental analytical methods.

The authors present the results verifying the structure of each of these compounds. The methods for qualitative and quantitative analysis of these compounds were developed in the study. The HPLC validation was performed for the LCS-1269 quantification method. The study showed the compliance of the obtained validation characteristics with the criteria approved by the Russian State Pharmacopoeia XV Ed and Pharmacopoeia of the Eurasian Economic Union. The authors determined the structure of impurities in LCS-1269 samples and proposed a method for their quantitative determination.

Conclusion. Structures of indolo [2,3-a] carbazole derivatives LCS-1208 and LCS-1269 were confirmed and shown to be reliably distinguishable. Impurity structures from the final LHS-1269 synthesis step were identified. HPLC methods for quantifying LCS-1208 and LCS-1269 were developed.