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Aim. To determine informative prognostic criteria for assessing the HER2 / neu status in primary breast cancer using 99mTc-DARPinG3.Materials and methods. The study included 10 patients with breast cancer (T1-4N0-2M0) before systemic therapy, who underwent a radionuclide study using 99mTc-DARPinG3 at a dose of 3,000 μg. Five patients were characterized by HER2 / neu overexpression in primary breast cancer, whereas 5 patients were HER2-negative. For all patients, morphological and immunohistochemical studies and fluorescence in situ hybridization (FISH) of the primary tumor nodule were carried out. Single-photon emission computed tomography (SPECT) of the chest was performed for all patients 4 hours after the injection of 99mTc-DARPinG3.Results. The total activity of 99mTc-DARPinG3 was 522.4 ± 341.8 MBq. The comparative analysis showed that higher uptake of the labeled protein in HER2-positive breast cancer was significant (p = 0.0159, Mann – Whitney U test). The analysis of the ratios showed significant differences in the tumor-to-background ratios in patients with HER2-positive breast cancer (p < 0.0159, Mann – Whitney U test). Based on the logistic regression analysis, a mathematical model was developed to predict the status of HER2 / neu in primary breast cancer patients (specificity and sensitivity 100%; p = 0.0004) using 99mTc-DARPinG3 at a dose of 3,000 mcg 4 hours after the injection of the radiopharmaceutical.Conclusion. The results of the study allow to consider the tumor-to-background ratio 4 hours after the injection of 99mTc-DARPinG3 as an additional prognostic parameter for determining the HER2 / neu status in primary breast cancer.

HER2-positive breast cancer occurs in 15–20% of breast cancer patients and is associated primarily with a poor prognosis of the disease and the need for highly specific targeted therapy. Despite the clinical importance of determining HER2/neu, traditional diagnostic methods have their disadvantages and require the study of new additional research techniques.The information presented in this review makes it possible to consider current trends in the radionuclide diagnosis of HER2-positive breast cancer using the latest class of alternative scaffold proteins and to consider various aspects of their use in clinical practice.

Introduction. Overexpression of Her2/neu is detected in 15–20 % of patients with breast cancer and associated with an aggressive form of disease and low overall and disease-free survival rates. Currently, immunohistochemical studies (IHC) and methods of in situ hybridization are used to assess Her2/neu status. One of significant drawbacks of this detection is the impossibility of simultaneous assessment of the receptor status of the primary tumor and metastatic sites. The increasing popularity of radionuclide methods using recombinant proteins as a targeting module have already demonstrated their effectiveness in solving this question at the initial stages of clinical research.The purpose of this study is to demonstrate a clinical case of assessing the extent of breast cancer in a patient with overexpression of Her2/neu using a radiopharmaceutical based on targeted protein molecules labeled with technetium-99m.Description of the clinical case. A patient diagnosed with stage IIIA right breast cancer (T2N2M0), multicentric growth and metastases in right axillary and subclavian lymph nodes at the diagnostic stage was injected intravenously with 99mTc-ADAPT6 radiopharmaceutical. The drug was prepared in the Department of Nuclear Medicine of Research Cancer Institute (Tomsk) immediately before its administration. Planar scintigraphy and singlephoton emission tomography of the chest organs were performed 2 hours after injection of 99mTc-ADAPT6 radiopharmaceutical. In addition to the previously described tumors, 3 foci of hyperfixation of the tracer in the projection of the 5th rib on the right along the middle-clavicular line, as well as in the projection of the 8 and 9 thoracic vertebrae (Th VIII, IX) were found. Computed tomography of the chest organs and bone scintigraphy with 99mTc-pyrophosphate showed no metastases in the 5th rib on the right and Th VIII, IX. Magnetic resonance imaging of the thoracic spine revealed 2 metastatic foci in Th VIII, IX. Planar scintigraphy with 99mTc-pyrophosphate and CT performed 6 months after injection of 99mTc-ADAPT6 revealed previously described foci in the projection of the thoracic spine (Th VIII, IX) and 5 ribs on the right along the mid-clavicular line. Conclusion. The results demonstrated during the study suggest that 99mTc-ADAPT6 is a promising tracer for molecular imaging of tumor foci with overexpression of the Her2/neu receptor in breast cancer patients.

Background. The chief goal in assessing the Her2/neu status in clinical practice is to identify indications for targeted therapy. The main methods for determining the Her2/neu status are an immunohistochemical method and fluorescence in situ hybridization (FISH); however, despite their widespread use, they have a number of significant disadvantages. Over the past few years, radionuclide diagnosis using a new class of alternative scaffold proteins that meet all the requirements for optimal radionuclide delivery to tumor cells has become widespread.Objective: comparative analysis of the effectiveness of radionuclide imaging of Her2-positive breast cancer using 99mtechnetium-labeled recombinant molecules in different dosages. Material and methods. The investigation enrolled 22 patients with breast cancer (T1-4N0-2M0) before systemic therapy: 11 had Her2/neu overexpression; 11 had no marker expression. The patients’ mean age was 50.7 ± 2.3 years. Morphological and immunohistochemical studies were performed in all cases. FISHanalysis was carried out in the presence of the Her2/neu 2+ value. The agent was prepared immediately before using in dosages of 500 and 1000 µg, after which it was slowly administered intravenously to the patient. Whole-body scintigraphy and chest single-photon emission computed tomography were conducted at 2, 4, 6 and 24 hours after administration.Results. The radiochemical yield and radiochemical purity values were 77 ± 9% and 99 ± 1%, respectively. The activity of the agent immediately before administration was 416 ± 135 MBq for the 500 µg group and 349 ± 133 MBq for 1000 µg group. Analysis of the findings indicated that the higher uptake of the agent by organs without tumor lesion was observed in the kidneys, liver, and lungs. The highest renal absorption of the agent was observed in both study groups (0.135 ± 0.042 and 0.191 ± 0.047 mGy, respectively). The effective dose was 0.009 ± 0.002 mGy for the 500 µg group and 0.010 ± 0.003 mGy for the 1000 µg group. The better distribution between the tumors with Her2/neu positive and negative statuses was observed 2 hours after administration in the 500 µg group with the mean tumor/background value of 37 ± 19 for Her2-positive tumors, and 5 ± 2 for Her2-negative tumors (p < 0.001).Conclusion. The findings suggest that the test radiopharmaceutical agent at a dose of 500 µg can be considered as a new additional method to diagnose Her2-positive breast tumors.

Background. The main purpose of the Her2/neu status determination in clinical practice is to determine the indications for the appointment of targeted therapy. The main methods for detecting the Her2/neu status are the immunohistochemical method (IHC) and the fluorescence in situ hybridization (FISH); however, despite their widespread use, they have a number of significant disadvantages. Over the past few years, radionuclide diagnostics using a new class of alternative scaffold proteins that meet all the requirements for optimal delivery of radionuclides to tumor cells has become widespread.Aim. To study the possibility of clinical use of a radiopharmaceutical based on technetium-99m-labeled target molecules for the diagnosis of breast cancer with the Her2/neu overexpression in humans.Materials and methods. The study included 11 patients with breast cancer (T1–4N0–2M0) before systemic therapy: 5 with Her2/neu overexpression; expression of the marker was not detected in 6. In all cases, morphologicaland immunohistochemical studies were performed. In case of Her2/neu 2+, FISH analysis was performed. The radiopharmaceutical was prepared immediately before administration, after which it was slowly injected intravenously into the patient. Scintigraphic studies in the “WholeBody” mode and SPECT of the chest organs were performed 2, 4, 6 and 24 hours after injection.Results. Radiochemical yield, radiochemical purity and activity before administration were (80 ± 4)%, (98 ± 1)% and (434 ± 19.5) MBq, respectively. The greatest uptake by normal organs was observed at a time interval of 6 hours in the kidneys and at a moderate activity in the liver and lungs at the same time interval. The organ with the highest absorbed dose was the kidneys; significant accumulation was also detected in the adrenal glands, gallbladder, liver, pancreas and spleen. The smallest accu mulation of the studied drug was observed in the brain (0.001 ± 0.000) mGy and skin (0.001 ± 0.000) mGy. The effective dose was (0.009 ± 0.002) mGy. The difference between tumors with positive and negative Her2-neu expression was found at all time points. In this case, the best indicator was determined after 2 hours of drug injection (р < 0.05).Conclusion. Based on the results obtained, it can be indicated that the investigated radiopharmaceutical can be considered as a new additional method for the diagnosis of Her2-positive breast tumors.

Epidermal growth receptor HER2/neu is still of great interest, the overexpression of which is most often observed in patients with breast cancer and accounts for 15–20 % of cases. Present methods of HER2/neu determination have a number of significant drawbacks. In recent years, alternative framework proteins are used for the targeted radionuclide imaging. Molecules of DARPin (Design Ankyrin Repeat Protein) are one of representatives of scaffolds. Material and methods. The study included 4 breast cancer patients (T1-2N0-1M0) who were not receiving systemic therapy at the time of the study: in 2 patients, HER2/neu overexpression was noted, in 2 patients – not detected. HER2/neu status was determined using an immunohistochemical method and a FISH assay. At the preclinical stage, radiopharmaceutical 99mTc-DARPin9_29 was injected intravenously to all patients, «WholeBody» scintigraphy and single-photon emission computed tomography were performed 2 hours after injection. Results. The distribution of radiopharmaceuticals in organs 2 hours after injection revealed the greatest accumulation in the liver and kidneys. In studying of tumor/background indicator it was revealed that values of the studied parameter in patients with overexpression of HER2 receptors are more than 3 times higher than the values in the subgroup of patients with negative expression of this marker. Conclusion. According to the results of preliminary studies, the 99mTc-DARPin9_29 demonstrated significant differences between tumors with and without HER2/neu overexpression.

Now widely discussed question, both at the national level, and in popular scientific literature attempt of change of structure of the Russian economy for benefit of forming of high-tech industries is, thereby, creating transition from raw to innovative model of development. This circumstance is very actual as it is implemented in line with universal tendencies of high-quality updating of technological base of production on the basis of modern developments in the field of nano - and biotechnologies, energy saving, the advanced information, communication systems, etc. In this article the role of innovations and technologies in development of entrepreneurial structures of production and industrial sector on the example ofJSC Gazprom is considered.

Formation of a market management mechanism in the Russian economy objectively requires strengthening the role of logistics in general and in the restructuring of the automotive industry in Russia in particular. In the article the main reasons that caused such an interest in the analysis is the automotive industry.Methodology. The methodological basis of this article are comparative, economic and statistical analysis methods.The purpose of this article is to reveal the key theoretical and practical issues of the role of logistics in the restructuring of the automotive industry companies, taking into account global transformations occurring in the world economy. This has allowed to specify the main issues associated with the use of logistics in the restructuring of the automotive industry in Russia.Conclusions. The following conclusions were obtained: research in the field of restructuring of the automotive industry enterprises are considered in the most general terms as "any changes to the strategic nature of the enterprise"; The second approach – the authors in their definitions focus on the restructuring of its individual aspects – goals, directions and forms of restructuring.

The subject / topic. The relevance of the article is that today tourism is a massive social and economic phenomenon of global scale, as is known, any vacation begins with advertising. Therefore, for the progressive development of tourism companies need to develop an eff ective strategy and tactics of advertising projects. Potential consumers have become more discerning and prudent, so a consultant position with the fl ood of information does not work. Works expert position, when the product is as if created for the client, that is, the product exists only in synchronism with the buyer. In view of this increased competition between operators of tourist services, and certain segments of the market saturation of a significant amount of travel products with a similar orientation, a unique role for the positioning on the basis of marketing strategy as a process for creating a unique tourism product in the market.The purpose / goal. The aim of the article is to study the features of the marketing strategies of advertising processes in the market of travel agencies and find directions of their improvement in current economic conditions.Article Objectives: To investigate the nature and content of the concept of "marketing strategy of advertising processes"; systematize criteria for the classification of the Company's strategy in the market of tourist services; analyze the features of advertising projects and identify promising directions for improving the marketing strategies.Methodology. The methodological basis of this article are comparative analysis methods.Results. The essence and content of the concept of "marketing strategy of advertising processes." The features of the market of tourist services, allocated target audiences, identifies key factors and trends in the development of this market.The new system is a product of values, square S. Kovalev, who identified four existing mentality of the person. When advertising article or video include representative words and phrases that use all four levels of mentality, because of this advertising always achieves goals.Conclusions / relevance. Promising further expansion of the practice of implementation of marketing approaches in the organization of work of the subjects of the tourism sector, including the use of new technologies.Practical application of the results of this work will form a favorable image of the tourism industry, its products and, ultimately, create positive social and economic eff ect.

The subject / topic: The level of development of any country is currently determined by the proportion of high technologies in the GDP. Logistics – the basis for efficient management of modern knowledge-intensive production. Given the adverse conditions in the global economy, greatly enhanced the relevance of the study of logistical aspects in the management of high-tech products.Subject of research: The logistics management of production of high technology products in turbulence changing global economy. In this paper we apply scientific methods: the dialectic, comparisons and analogies, analysis and synthesis, deduction and induction, abstract , logical, historical and retrospective. The purpose of this article is to identify the characteristics and problems of logistics management of production of high technology products in the countries of the Customs Union and the Eastern Partnership. Also consider the role of clusters in the formation of innovation infrastructure in the countries of the Customs Union.Results: As part of the presentation was the author of the present article the urgency of application of CALS-technologies as a tool for organization and information support for the creation, production and operation of the product at the enterprises of the national economy.Conclusions / significance: Management of enterprises in the real sector of the economy in modern conditions should be based on synergies methodological principles of market and state regulation, with increased use of methods focused on the long term. By such methods, in particular, should include the methods of logistic management of production of high technology products. The importance of these technologies has increased steadily, and in modern conditions gets a new quality content that refl ects the phased development plan targeted action to ensure that the desired state of the enterprise as a socio-economic system. This in turn points to the need to ensure that new scientific technologies, procedures and practices of the logistics management of production of high technology products, which can be designed to ensure a relatively stable crisis-free development of the enterprise.