Studying the General Toxicity and Cumulative Properties of a Radiopharmaceutical Nanocolloid, (99m)Tc-Al2O3.

We studied toxicity of a new Russian radiopharmaceutical Nanocolloid, (99m)Tc-Al2O3. Tests for acute toxicity showed that this agent belongs to a class of moderate-toxicity substances and does not have cumulative properties. The evaluation of subchronic toxicity after subcutaneous injection of this product to rats (0.04, 0.2, and 0.4 ml/kg) and rabbits (0.02 and 0.2 ml/kg) for 7 days did not reveal changes in the general state, temperature, body weight, indices of the peripheral blood and bone marrow, functions of the heart, liver, kidneys, and nervous system, and morphological characteristics of the internal organs in animals. The drug does not produce a local irritant effect.

[Optimization of the extent of surgery in organ- preserving treatment for invasive cervical cancer (the role of sentinel lymph nodes study)].

The study included 44 patients with Stage Ia1 - lb1 cervi- cal cancer who underwent organ-preserving surgery (transab- dominal trachelectomy). To visualize sentinel lymph nodes - lymphoscintigraphy with injection of radioactive lymphotropic isotope - (99m)Tc-labelled nanocolloid was injected a day before surgery. Intraoperative identification of sentinel lymph nodes using gamma probe was carried out to assess, which lymph nodes had taken up the radionuclide. Detection of sentinel lymph nodes in cervical cancer patients could accurately predict the pelvic lymph node status, assess the stage of the dis- ease, individualize the extent of surgery and determine indica- tions for organ-preserving surgery.

[Radioimmunotherapy: current state of the problem].

This review presents modern data about one of the promising direction in treatment of malignancies, which is called radioimmunotherapy. The special attention is paid to search of new targets and development of radiopharmaceuticals that will allow improving quality and accuracy of the directed impact on tumors of various localizations.

[Barotherapy in the military medicine].

Barotherapy in the military medicine. The authors present current data on place and role of hyperbaric oxygenation for military and extreme medicine. Main mechanisms of oxygen saturation and its <> to cells and tissues of the organisms is described in the given article. The authors proved advantages of the hyperbaric oxygenation over the normobaric and showed its high efficiency for the trauma and suppurative- septic lesion treatment, and for the combat therapeutic pathology. Main clinical and physiological effects of the hyperbaric oxygenation are showed. Modern indications and contra-indications for the use of the hyperbaric oxygenation as a therapeutic mean are proved.

[Radionuclide Methods in the Assessment of Anthracycline-Induced Cardiotoxicity].

PURPOSE: To compare diagnostic efficacy of multigated acquisition (MUGA) scan and Tc-99m MIBI gated SPECT for evaluation and forecast of anthracycline-induced cardiotoxicity. MATERIAL AND METHODS: We included into this study 80 patients (72 women and 8 men, mean age 43 ± 4.2 years) with malignant tumors without overt pathology of the cardiovascular system. These patients received doxorubicin (50 mg/m2 per course) based cytostatic therapy. All patients were studied either by MUGA (n = 40) or 99MTc MIBI gated SPECT (n = 40) before initiation of chemotherapy 1 hour after first administration of doxorubicin and after the 4th course. RESULTS: After administration of 50 mg/m2 of doxorubicin 14 patients according to MUGA scan and 16 patients according to 99mTc MIBI gated SPECT had significant (≥ 10%) reduction of left ventricular ejection fraction (LVEF). Significant inhibition of systolic function in these patients remained after the 4th course of treatment. Individual analysis of the MUGA and 99mTc MIBI gated SPECT data registered after the fourth course (achievement of total doxorubicin dose of 200 mg/m2) showed that ≥ 10% LVEF reduction in response to the first dose of doxorubicin could predict the development of cumulative cardiotoxicity. CONCLUSION: MUGA scan and 99mTc MIBI gated SPECT can be applied with equal effectiveness for assessment of acute and chronic anthracycline-induced cardiotoxicity in patients with malignant tumors. LVEF reduction ≥ 10% in response to the first dose of doxorubicin appeared to be a predictor of development of chronic cardiotoxicity.

[STUDYING ACUTE TOXICITY OF NEW RADIOPHARMACEUTICAL 99MTC-AL2O3 NANOCOLLOIDS FOR ONCOLOGICAL DIAGNOSTICS].

The acute toxicity of a new drug based on nanocolloidal gamma alumina labeled with technetium-99m (99mTc) has been studied on 80 rats (40 females and 40 males) and 80 mice (40 females and 40 males) with intraperitoneal and subcutaneous drug administration. A single administration of the pharmacological agent was followed by observation of the survival of animals for 14 days with determining tolerable, toxic, and lethal doses for intraperitoneal and subcutaneous administration according to the Litchfield - Wilcoxon method, establishing the causes of animal death within 14 days of observation, and studying the drug influence on the general condition and some functional and morphological indices. Based on the established boundaries of toxicity and the classification of toxicity, the 99mTc-Al2O3 nanocolloids can be classified into conditionally moderately toxic substances. The actual values of LD5 of the radiopharmaceutical fall in the range of large doses. The safety factor for the drug studied significantly exceeds the minimum permissible value of 100.

Evaluation of HER2/neu Expression in Metastatic Axillary Lymph Node Tissue of Breast Cancer Patients Using [99mTc]Tc-(HE)3-G3.

Anatomic visualization and molecular typing of metastatic regional lymph nodes in breast cancer patients are a serious clinical challenge in modern oncology. According to the results of previous studies, [99mTc]Tc-(HE)3-G3 has proven to be a promising diagnostic agent in differentiating the HER2/neu receptor status in primary breast tumors (p < 0.05, Mann-Whitney test). In this regard, the purpose of this study is to explore the possibilities of using [99mTc]Tc-(HE)3-G3 to determine the HER2/neu receptor status in the metastatic axillary lymph nodes (mALNs) of breast cancer patients. The study was conducted using clinical material from 20 breast cancer patients (T2-4N1-3M0-1) before systemic therapy (10 patients with positive and 10 patients with negative HER2/neu expression in mALNs) who underwent SPECT/CT scan 4 h after the administration of [99mTc]Tc-(HE)3-G3. Morphological and immunohistochemical studies of mALNs with assessment of the HER2/neu status were performed on all patients. We found that mALN-to-background and mALN-to-latissimus dorsi muscle ratios for [99mTc]Tc-(HE)3-G3 uptake 4 h after its administration may be used for typing of the HER2/neu status in mALNs of breast cancer patients (p < 0.05, Mann-Whitney test). In that case, sensitivity and specificity for the mALN-to-background ratio were identical at 80%, with the threshold value being > 12.25.

[Determination of divers' resistance to decompression gas formation].

The aim of the study was to determine the correlation between the state of the individual functions of the organism and the intensity of decompression venous gas embolism after high air pressure exposure. The analysis of the guidelines defining the procedure of divers' medical examination was made and 320 divers were surveyed. Indices of the divers' central nervous and cardiovascular systems were measured before and after their immersion into a hyperbaric chamber. The study found that the conduct divers' on-resistance to unfavorable scuba dive should be provided by the military-medical commission, so the position of diving doctor should be put to it staff. It was revealed that the rate of simple visual-motor reaction, measured before the diving can serve as an indicator of human resistance to decompression gassing. The formula for determining the stability of decompression gassing of men aged 20-30 years in terms of state of organism functions was proposed.

[Effect of combined modality treatment with intraoperative radiotherapy on the morphofunctional state of the myocardium in patients with stage-III lung cancer].

Epy influence of combined treatment including neoadjuvant chemotherapy, radical surgery and intraoperative radiotherapy with a single dose of 15 Gr or 10 Gr has been studied in conditions of radiosensibilization on morphological and functional status of myocardium in non-small lung cancer patients at stage III with by means of ECG-synchronized single-photon emission computed tomography of myocardium with 99mTc MIBI. It was shown that this kind of treatment does not worsen functional status of myocardium, besides the perfusion level of myocardium correlated with initial concomitant cardiovascular pathology and extent of surgical treatment.

The Evolution of Targeted Radionuclide Diagnosis of HER2-Positive Breast Cancer.

This review examines the evolution of the radionuclide diagnosis of HER2-positive breast cancer using various compounds as a targeting module in clinical practice: from full-length antibodies to a new group of small synthetic proteins called alternative scaffold proteins. This topic is of especial relevance today in view of the problems attendant to the detection of breast cancer with HER2/neu overexpression, which, in most cases, introduce errors in the treatment of patients. The results of clinical studies of radiopharmaceuticals based on affibody molecules, ADAPTs, and DARPins for SPECT and PET have demonstrated good tolerability of the compounds, their rapid excretion from the body, and the possibility to differentiate tumor sites depending on the HER2/neu status. This indicates that targeted radionuclide diagnosis holds promise and the need to continue research in this direction.