Russian Scientific Center of Radiology and Surgical Technologies

The article is devoted to synthesis, identification and investigation of cytotoxicity for graphene oxide (GO) conjugate with cytostatic agents such as SN38 (7-Ethyl-10-hydroxycamptothecin, (4S)-4,11-Diethyl-4,9-dihydroxy-1,4-dihydro-3H,14H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14-dione) and Exatecan mesylate (ExMes, (1S,9S)-9-Ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzopyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-1-amine methanesulfonate). GO was synthesized via a modified Hummers and Offeman method, resulting in the production of GO enriched with oxygen-containing functional groups. The obtained nanomaterial was covalently functionalized with cytostatic agents and characterized using 13C Nuclear magnetic resonance (NMR), Raman and Infrared (IR) spectroscopy, X-ray diffraction (XRD), High-resolution transmission electron microscopy (HRTEM), and Dynamic light scattering (DLS) techniques for aqueous dispersions. The biocompatibility assessment included an evaluation of cytotoxicity toward PANC-1, HeLa, and HEK293 cell lines, as well as study of mechanisms of endocytosis.

Aim. To analyze the efficacy and safety of combining nivolumab with AVD chemotherapy (N-AVD) in patients with newly diagnosed classical Hodgkin’s lymphoma in real-world evidence studies.Materials and methods. The retrospective single-center study included 26 patients (14 men, 12 women) with advanced disease stages (IIB with unfavorable prognostic factors according to GHSG (German Hodgkin Study Group) or III–IV according to the Ann Arbor classification). Patients received therapy at the Leningrad Regional Clinical Hospital from March 2023 to February 2025. The N-AVD regimen included nivolumab at a dose of 3 mg / kg (maximum 240 mg), doxorubicin 25 mg / m2, vinblastine 6 mg / m2, and dacarbazine 375 mg / m2 on days 1 and 15 every 28 days. Patients with stage IIB were planned to receive 4 cycles of N-AVD, in case of stages III–IV – 6. Some patients received consolidating proton therapy – 6 (24 %) or 3D conformal radiation therapy – 6 (24 %). The primary endpoint of the study was progression-free survival, and secondary endpoints were the complete remission rate, safety, event-free survival, and overall survival.Results. The complete remission rate was 94 %. With a median follow-up of 11.9 months, 1‑year progression-free survival was 95.7 %, and overall survival – 100 %. The most common adverse events were grade 3–4 neutropenia (46.2 %) and febrile neutropenia (11.5 %). Immune-mediated complications represented by two cases of hypothyroidism and acute pericarditis in one patient.Conclusion. Preliminary results of our study demonstrate the high efficiency of the N-AVD regimen and emphasize the importance of monitoring immune-mediated complications. The advisability of consolidation radiotherapy in patients with complete remission on anti-PD1 monoclonal antibody therapy requires further study. Our study confirms the prospects of using the N-AVD regimen in patients with newly diagnosed classical Hodgkin’s lymphoma, but longer follow-up and a larger sample are needed for conclusions.

Introduction. The study of lymphatic collectors state in oncological practice is important primarily for identification of prevalence of the pathological process. Various changes in the structure of the lymph nodes (LN) both in benign conditions and in cases of malignant lesions can have similar ultrasound (US) characteristics. The difficulty in interpreting US picture of LN is that there are no clear criteria for differentiation of these conditions. The proposed Russian project of Lymph-NodeRADS.RU classification presents a step-by-step assessment of U S characteristics of the LN by categories with mandatory consideration of the clinical history and the patient’s oncological history.Aim. To determine the most significant US criteria for a standardized analysis of risks for malignant pathology of the superficial LNs with subsequent distribution into types according to the Lymph-NodeRADS.RU.Materials and methods. A retrospective analysis of echograms of 246 surface LNs from 3 anatomical zones was performed: 155 head / neck, 56 axillary, 35 inguinal. Of these samples 71 were without and 175 were with malignant lesions. The presence and nature of 209 LN lesions were confirmed by morphological studies (cyto- or histological, including immunohistochemical assessments), of 37 – by clinical and laboratory parameters. The Random Forest machine learning method was used to determine significance of LN US parameters. The Mean Decline Accuracy criterion was used to quantify the effect of the traits.Results. There is no US sign indicating a malignant process in the LN with a probability of 100 %. The greatest significance for the diagnosis of LN malignant lesions is a set of criteria: irregular or rounded shape, roundness index, fuzziness and discontinuity of the border, angular contours, impaired differentiation of echostructure and the presence of pathological inclusions, peripheral or mixed types of blood flow. Stratification of the LN US criteria by Lymph- NodeRADS.RU classification types revealed risk of malignancy of categories 1 and 2 in 0 % of cases, category 3–45.1 %, category 4–85.3 %, category 5–96.6 %.Conclusions. For objective US assessment of surface LN, it is necessary to use a set of both qualitative and quantitative US characteristics. When employing the classification of Lymph-NodeRADS.RU it is necessary to take into account anamnestic and clinical data, especially in the case of a dubious US pattern of LN.

MICA/B molecules (MICs) are stress-induced molecules expressed by infected and tumor cells. Their expression also characterizes trophoblast cells. Cytotoxic lymphocytes, including natural killer (NK) cells, express the NKG2D receptor, aiding them in the recognition and destruction of target cells that present MICs. To evade destruction, target cells employ various defense mechanisms, including the secretion of soluble forms of MICs. Choriocarcinoma JEG-3 cells and NK-92 cells were used to assess the expression of MICs and NKG2D. The cytotoxicity of NK-92 cells against JEG-3 cells in the presence of trichostatin A (TSA), anti-MICA/B antibodies (anti-MICA/B), and recombinant MIC proteins (rMICA/B) was evaluated. JEG-3 cells and NK-92 cells express MICs. Additionally, NK-92 cells exhibit high levels of NKG2D receptor expression. TSA treatment reduced the surface expression of MICs on choriocarcinoma cells, and was also associated with the release of soluble MICB. However, the TSA-induced decrease in MIC expression by choriocarcinoma cells did not protect them from the cytotoxic effects of NK cells. Only the activation of NK cells by IL-12 resulted in a decline in susceptibility of TSA-treated choriocarcinoma cells to NK cell-mediated cytotoxicity. Thus, NK cells activated by IL-12 lose their ability to effectively kill TSA-treated choriocarcinoma cells through the MIC-mediated mechanisms.

The development of nuclear medicine has led to an increase in the use of open radionuclide sources and the associated processes of transporting ionising radiation sources and generating radioactive waste. This situation leads to focus on monitoring and accounting of ionising radiation sources in hospitals. The aim of the study was assessment of geographical distribution and structure of nuclear medicine centres in theRussian Federation. Material and Methods: The register of sanitary and epidemiological conclusions on the compliance (non-compliance) of activities (works, services) with the requirements of state sanitary and epidemiological rules and regulations were analyzed at the beginning of 2025. Results: 188 hospitals operated with radionuclide, are located in the Russian Federation in 2025, including 152 single photon diagnostic nuclear medicine departments (38 in Moscow and 20 in St. Petersburg); 81 positron emission tomography departments (26 in Moscow and 8 in St. Petersburg); 52 radiopharmaceutical therapy departments (12 departments in Moscow and 5 in St. Petersburg). According to the results of the study, all radiopharmaceutical therapy departments are based in diagnostic nuclear medicine centers. Conclusion: The current practice of organizing radiopharmaceutical therapy units based on diagnostic nuclear medicine units does not allow to consider the radiation safety issues separately for diagnostics and therapy. It is reasonable to have uniform requirements for nuclear medicine units

Pancreatic neuroendocrine tumors (PNETs) are frequently asymptomatic (in >50% of patients) and are diagnosed at stage IV, typically with synchronous liver metastases. Patients with initially unresectable PNETs presenting with massive liver involvement, systemic intoxication, and multiorgan failure face poor prognosis and often have contraindications to antitumor therapy. We present a clinical case of a female patient followed in St. Petersburg medical institutions since 2009 for multifocal liver lesions initially diagnosed as «hepatic hemangiomatosis». Since January 2016, she has been managed at the A. M. Granov Russian Research Center with diagnosis: PNET G2 T3N1M1 (>80% liver involvement). At initial diagnosis, her condition was graded as severe (ECOG 3) with rapid deterioration due to progressive hepatic failure. The clinical complexity was compounded by contraindications to systemic therapy. The patient received a center-developed treatment algorithm incorporating locoregional approaches. Following treatment, partial response was achieved, allowing treatment-free interval from October 2021 to July 2024, after which systemic therapy was initiated. Currently, the patient is asymptomatic with satisfactory performance status (ECOG 0–1).

Objective. To analyze the data of patients with kidney cancer complicated by tumor venous thrombosis of the renal vein and inferior vena cava of levels 1–2 who underwent laparotomic and laparoscopic surgical treatment. Materials and methods. A study of 100 patients diagnosed with kidney cancer complicated by tumor venous thrombosis of the renal vein and inferior vena cava of levels 1–2 was conducted at Russian Research Center for Radiology and Surgical Technologies named after Academician A.M. Granov in the period from 2007–2024. 50 (n = 50) patients underwent open surgery, and the rest 50 (n = 50) patients underwent laparoscopic surgery. In the group of patients with laparoscopic surgery, in 8 (n = 8) patients, conversion of approach was performed which resulted in tumor thrombus invasion into the inferior vena cava (IVC) wall; adhesive disease; uncontrolled bleeding. Results. The median duration of laparoscopic surgery was 127.5 (115–155) min and surgery with laparotomy approach –132.5 (110–155) min, p = 0.4006. The median volume of blood loss in endoscopic approach was 200 (150–300) ml, in laparotomy – 250 (200–350) ml, p = 0.0105. Postoperative complications of the first class according to the Clavien–Dindo classification were observed in 20 patients (20 %), those of the second class were in 8 patients (8 %), 3 patients (3 %) had the third-class severity and the 4th class severity was noted in 2 patients (2 %). The median duration of hospital stay was 9 days for open surgery (8–10) and 7 days in laparoscopy (7–8), p 0.001. Conclusions. The data of the conducted study demonstrate the effectiveness of classical nephrectomy with thrombectomy for patients diagnosed with kidney cancer complicated by tumor venous thrombosis of the renal vein and inferior vena cava of levels 1–2. Conventional laparotomic nephrectomy with thrombectomy is the gold standard for the treatment of locally advanced renal cell cancer in stage pT3a and pT3b, but laparoscopic approach acts as an effective alternative. The above study clearly demonstrates it.

Exosomes are spherical extracellular nanovesicles of endosomal origin, whose function is to encapsulate part of the contents of the parent cells producing them and transport this content to the target recipient cells using biological fluids. Due to their properties, exosomes are considered as potential biological drug delivery systems. For medical purposes, exosomes are isolated from various natural sources. The use of each type of exosome for therapeutic purposes has its advantages and is associated to varying degrees with several biological (stability, immunogenicity, toxicity) and technical (production scaling-up, standardization of isolation protocols, drug loading) problems. Exosomes derived from human cells have significant potential as therapeutic drug (TD) delivery vehicles due to their endogenous origin. However, simultaneously with the delivery of TD, they can carry potentially dangerous biomolecules. Farm animal milk-derived exosomes and exosome-like plant-derived extracellular vesicles have enormous therapeutic potential in themselves and are safe as drug delivery vehicles. However, data on their effects on the human body are limited. Artificial exosomes created with the help of nanobiotechnology can overcome many of the technical limitations inherent in natural exosomes. The review discusses the strengths and limitations of different types of natural and artificial exosomes as drug delivery nanocarriers, as well as challenges associated with their implementation in clinical practice.

Patients undergoing radionuclide therapy with radiopharmaceuticals may become a radiation source of external exposure. Release of the patients requires strict abidance of radiation safety regulations to minimize exposure to individuals in contact with patient, especially children and pregnant women. The purpose of the current study was to determine precautions for patients after radionuclide therapy to limit the contact time with others and to develop guidelines to reduce doses to individuals in contact with patient. Two cases were considered for analysis: contact with young children and co-sleeping with partners. Determination of the necessary time limitations was performed using open-assessed publications and Monte Carlo calculations at different distances from the patient. The results showed that radionuclide therapy with 225Ac, 223Ra, 89Sr, and 90Y would not exceed the limit of 0.3 mSv to individuals in contact with patient after radionuclide therapy, even in the case of no precautions. However, for patients with 131I, 177Lu and 153Sm, precautions to limit the time of close contact with children and co-sleeping with partners are required. The suggested precautions ensure the radiation safety of individuals in contact with the patient after radionuclide therapy by limiting the exposure limits and allow patients to maintain social contacts, which is important for their rehabilitation.