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.

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.

[Radionuclide teranostic of malignancies].

This review shows some basic information regarding the relatively new and one of the promising areas, called "theranostics' and also discusses its basic principles. Special attention is paid to the study of approaches in selecting the most appropriate in the application of radioisotopes for solutions appropriate diagnostic and therapeutic applications. Also presented the main directions in the work with monoclonal antibodies and their use in radionuclide theranostics.

[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.

[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.

[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.

[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.

[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.

[Different types of 199Tl chloride scintigraphic visualization of malignant tumors of the locomotor apparatus].

BACKGROUND: 201Tl chloride scintigraphy allows malignant tumors of the locomotor apparatus to be diagnosed. The capacities of scintigraphy with 199Tl chloride, a 201Tl chloride analog, in addition to routine visualization of malignant tumors of the locomotor apparatus, have revealed its untypical variants. OBJECTIVE: to study the specific features of 199Tl chloride scintigraphic visualization of malignant tumor processes in the locomotor apparatus. SUBJECTS AND METHODS: 199Tl chloride scintigraphy was performed in 85 patients having 107 foci of involvement presented with malignant (n = 57) and benign (n = 50) tumor processes. RESULTS: Malignant tumors were scintigraphically visualized in 98.1% of cases. Three types of their visualization were identified and studied; these included positive (82.4%) and rare: negative (7.8%), and mixed (9.8%) types associated with the specific features of the histological structure, metabolism, and blood supply of neoplasms and with the pharmacodynamic features of 199Tl chloride. The negative and mixed types, unlike metastatic neoplasms, were highly specific to primary or recurrent malignant tumors. CONCLUSION: Consideration of the negative and mixed types of scintigraphic visualization in addition to routine positive one permitted the sensitivity of diagnosis of malignant locomotor tumors to be increased from 90.4 to 98.1%, without reducing the specificity of 199Tl chloride scintigraphy.

[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.

[Scintigraphic evaluation of cerebral circulation in prognosis of cerebrovascular complications of coronary artery bypass grafting].

The aim of the work was to study the possibility of using single-photon emission computed tomography (OECT) of brain using 99m Tc-hexamethyl propylene aminoxime for the evaluation of long-term prognosis of the development of neurocognitive deficit after coronary artery bypass grafting (CBG) and elucidation of relationship between variations of cognitive function and regional cerebral circulation. Surgical myocardial revascularization under artificial circulation was performed in 22 patients with CHD. All of them were examined for the assessment of neurologic and neuropsychological status, and OECT data before, 14 days and 6 months after CBg. Early cognitive deficit developed in 96% of the patients and persisted for 6 months in 55%. Cognitive dysfunction was manifest as post-operative impairment of short- and long-term memory, and general efficiency of remembering. Visual memory and psychomotor speed also deteriorated. Cerebral circulation decreased in frontal and parietal lobes of the right hemisphere. Deterioration of long-term memory 6 months postoperatively correlated with the early circulation decrease of in the right and left temporal lobes.

[Cognitive dysfunction and brain perfusion in patients with arterial hypertension: possibilities of pharmacological therapy].

The study included 31 patients with essential hypertension. Twenty-four hours blood pressure monitoring, assessment of neurological status and cognitive functions as well as single photon emission tomography were performed at baseline and three months after treatment. The beta-blocker therapy during 3 months exerted a positive effect on the brain perfusion that resulted in the improvement of cognitive function - verbal and visual memory, attention, psychomotor speed, thinking and visuoconstruction.

[Gamma-scintigraphy in assessment cardioresynchronizing therapy at chronic heart failure].

The purpose of the work was to study influence of cardioresynchronizing therapy (CRT) on systolic and diastolic myocardial function with the aid of radionuclide methods. 19 patients (9 women) at the age from 21 to 72 years (average age 55.4 +/- 8.3 years) with NYHA class III - IV cardiac insufficiency, dilated cardiomyopathy (n = 14) and ischemic cardiomyopathy (n = 5) were included in the study. Radionuclide angiopulmonography and balanced radionuclide ventriculography were performed by standard method before CRT, in 20 - 30 days and in 12 - 18 months. In 20 - 30 days after CRT significant increase in stroke volume and stroke index, ejection fraction and part of circular fibers contraction was detected, which confirmed improve in systolic heart function. In 12 - 18 months significant increase in maximal filling rate index, filling fraction of 1/3 and 2/3 of diastole was noted, which reflected improve of left ventricle diastolic function. Recovery of myocardial contraction synchronism leaded to rehabilitation of normal pulmonary microcirculation. Radionuclide examination methods as high-informative modes of combine assessment of heart contractile function and pulmonary circulation in CRT dynamics are described. CRT, improving systolic and diastolic myocardial functions, has positive influence on pulmonary hemodynamics in patients with chronic heart failure.

[Experimental evaluation of the protective properties of some nonwoven materials for respiratory protection means and prospects of their use].

The protective properties of nonwoven materials (Spandbond, SMS) used to manufacture 3-5-layer medical masks, by using model physical and bacterial test aerosols, were experimentally assessed. It was shown that the more layers of the materials, the less permeable they became for test aerosols. Three-five-layer masks made from SMS at a density of 42 g/m2 were found to have higher protective properties for oil mist and fine aerosol than those made from Spandbond at a density of 25 g/m2. Five-layer SMS materials at a density of 42 g/m2 have the highest values of bacterial aerosol retention.

[Evaluation of the protective properties of nonwoven materials for throw-away medical overalls].

The permeability of varying density felts (Spandbond, SMS, Tyvek, Sontara) for throw-away medical overalls was experimentally assessed under statistic and dynamic conditions, by using model test aerosols, including bacterial one. Their permeability was shown to decrease with the higher density of the materials under study. Laminated Span-bond contributes to an abrupt reduce in the bacterial penetration of this kind of tissues and enhances their protective properties. The felts CMC, Tyvek, Sontara, and laminated Spanbond were found to have the highest protective properties. In terms of their barrier and protective properties, the felts surpass the tissues used to make re-usable protective medical overalls.

[Clinical experience of the use of autologous mononuclear bone marrow cells in patients with ischemic heart disease and dilated cardiomyopathy].

Between March 2003 and February 2005 cell therapy with mononuclear bone marrow cells (MBMC) was used in 38 and 4 patients with ischemic heart disease and dilated cardiomyopathy, respectively. Intracardiac administration of MBMC (87+/-12 millions) was carried out during coronary artery bypass surgery and/or left ventricular aneurysm resection (n=25) or in cardiac catheterization laboratory (n=17). For verification of cells fixation they were labeled with "Ceretec" 99mTc-HMPAO. Accumulation of labeled cells after 24 hours was 1.6+/-0.001%. After 6 months parameters of intracardiac hemodynamics and transitory myocardial perfusion defects improved significantly in all patients with ischemic heart disease.

[Scintigaraphic assessment of viability of the ischemic myocardium while carrying out nitroglycerine-mediated and orthostatic tests].

The work deals with diagnostic possibilities of single photon emission computed tomography (SPECT) of the heart and ECG-synchronized planar scintigraphy (ECG-PS) with 99mTc-tetrophosmine used to determine viability of the ischaemic myocardium in patients presenting with postmyocardium infarction cardiosclerosis. A total of 20 patients diagnosed with Ischaemic heart disease (IHD), functional class III-IV angina of effort, postmyocardium infarction cardiosclerosis were examined. All the patients underwent SPECT of the heart with 99mTc-tetrophosmine, which was carried out at rest and on the background of sublingual administration of nitroglycerine, as well as planar ECG-synchronized scintigraphy of the myocardium according to the protocol: rest - nitroglycerine-mediated - orthostatic tests. Repeat examinations at rest were performed 4-6 weeks after the coronary artery bypass (CAB). The obtained findings showed that sensitivity of perfusion SPECT with 99mTc-tetrophosmine of the myocardium amounted to 85%, specificity to 76%, and diagnostic accuracy to 82%. Calculating the diagnostic parameters of perfusion while using ECG-PS with sublingual administration of nitroglycerine demonstrated that sensitivity of the method amounted to 71%, specificity to 91%, and diagnostic accuracy to 83%. Analyzing the orthostatic test yielded sensitivity equalling 72%, specificity - 84% and diagnostic accuracy - 81%. Sensitivity of assessing myocardial contractility by means of ECG-PS using nitroglycerine amounted to 83%, with specificity of 86% and diagnostic accuracy of 85%. At the same time, sensitivity of the orthostatic test amounted to 80%, specificity to 92%, and diagnostic accuracy to 88%. Hence, carrying out SPECT and ECG-synchronized planar scintigraphy of the heart with 99mTc-tetrophosmine on the background of sublingual administration of nitroglycerine and the orthostatic test makes it possible to simultaneously assess the reserve of myocardial contractility and perfusion, thus strongly suggesting a high informative value of the techniques involved in detecting myocardial viability in patients with postmyocardium infarction cardiosclerosis.

Comparative scintigraphic study of 99mTc ciprofloxacin pharmacokinetics after intravenous and lymphotropic administration in experimental pulmonary suppuration.

Intravenously injected 99mTc ciprofloxacin is rapidly accumulated and washed from the septic focus. Lymphotropic injections provide targeted and long-lasting effect of the antibiotic. After injection into the interspinous ligament the drug slowly enters the inflammation area (by-passing the urinary organs and liver), where it is maximally accumulated only after 24 h, which allows to reduce the number of injections and the total dose of the antibiotic.