Co-production of 155Tb and 152Tb irradiating 155Gd / 151Eu tandem target with a medium energy α-particle beam.

INTRODUCTION: Four terbium isotopes 149,152,155,161Tb emitting various types of radiation can be used for both diagnostics and therapy. 152Tb emits positrons and is ideal for PET. 155Tb is considered a promising Auger emitter and a diagnostic pair for other terbium therapeutic isotopes. Several methods for the production of 155Tb using charged particle accelerators have been proposed, but they all have significant limitations. The restricted availability of this isotope hinders its medical applications. We have proposed a new method for production of 155Tb, irradiating enriched 155Gd by alpha particles. The possibility of simultaneous production of two isotopes of terbium, 152,155Tb, was also studied for more efficient cyclotron beam use. METHODS: Irradiation of 155Gd enriched targets and 155Gd / 151Eu tandem target with alpha-particles with an energy of 54 MeV was carried out at the U-150 cyclotron at the NRC "Kurchatov Institute". The cross sections of nuclear reactions on enr-155Gd were measured by the stack foil technique, detecting the gamma-radiation of the activation products. The separation of rare earth elements was performed by extraction chromatography with the LN Resin. 155Tb was produced via 155Dy decay. RESULTS: The cross sections for the 155,156Tb and 155,157Dy production were measured by the irradiation of a gadolinium target enriched with the 155Gd isotope with alpha-particles in an energy range of 54 → 33 MeV. The yield of 155Dy on a thick target at 54 MeV was 130 MBq/µAh, which makes it possible to obtain 1 GBq of 155Tb in 11 hour-irradiation with 20 µA beam current. The possibility of simultaneous production of 152,155Tb by irradiation of 155Gd and 151Eu tandem target with medium-energy alpha-particles is implemented. Optimal irradiation energy ranges of alpha -particles as 54 → 42 MeV for 155Tb and 42 → 34 MeV for 152Tb were suggested. Product activity and radionuclidic purity were calculated.

New method for production of 155Tb via 155Dy by irradiation of natGd by medium energy alpha particles.

INTRODUCTION: 155Tb (T1/2 = 5.32 d) is considered both as a promising Auger electron emitter and as a diagnostic pair for other therapeutic terbium radionuclides. Despite several methods for its production proposed, it remains scarcely available. Most of the methods using low-energy protons and deuterons beams result in a high content of radionuclidic impurities. High purity 155Tb can be obtained using high-energy proton beams combined with online mass separation of products, but the method remains inaccessible to most potential consumers. We have proposed an indirect method for the production of 155Tb via formation of 155Dy (T1/2 = 9.9 h), which can be implemented using medium energy alpha particles beam. METHODS: Gadolinium oxide targets of natural isotopic composition were irradiated by 60 MeV alpha particles beam on a U-150 cyclotron of the National Research Center "Kurchatov Institute". The cross sections of nuclear reactions were measured by the stack foil technique, detecting the gamma radiation of the activation products. Gd, Tb, and Dy were separated by extraction chromatography using the LN Resin sorbent in nitric media. The isolated dysprosium fraction was stored for a day, and the formed 155Tb was isolated by the same method. RESULTS: The cross sections for the formation of 159Gd, 153-156Tb, and 155,157Dy under irradiation by alpha particles of a gadolinium target of natural isotopic composition in the energy range 20-60 MeV have been measured. The 155Dy yield on a thick target at 60 MeV was 35 MBq/µAh, which makes it possible to obtain 1 GBq 155Tb as a result of 12-hour irradiation with a beam current of 50 µA. Extraction chromatography on LN Resin sorbent in nitric enabled quick and efficient separation of Gd, Tb, and Dy. The radiochemical yield of Dy was 95%, for Tb > 95%. The main radionuclidic impurity is 153Tb (T1/2 = 2.34 d; <5.4% of 155Tb activity). CONCLUSIONS: The developed method allows the production of therapeutic amounts of 155Tb with acceptable radionuclidic purity without the need for isotopically enriched materials. The amount of 155Tb is sufficient for its use in Auger therapy, as well as for preclinical studies of the suitability of SPECT preparations in laboratory animals. Nevertheless, to obtain higher activities, a longer irradiation time and a higher projectile current are proposed. The 153Tb radionuclide present in the final preparation has a shorter half-life than the target radionuclide, and its hard γ-lines have a probability of emission of less than 1%, from which it can be concluded that the negative effect will not be significant. However, a product of this purity and type of contamination requires additional testing for toxicity in living organisms. The final sample also includes a certain amount of 157Tb (T1/2 = 71 a, the only γ-line 54.5 keV Iγ = 0.0084%), which will complicate the labeling conditions. Thus, more research is needed in the labeling area. It should be noted that the use of gadolinium enriched in the 155Gd or 156Gd nuclide as a target will help not only reduce the amount of impurities but also increase the yield of 155Tb.

Cross sections of 3He-particle induced reactions on 186W.

Irradiation of 186W targets by 3He particles was carried out. For the first time the cross sections for the reactions of production of 183, 184, 186, 188Re, 183, 185Os, 187W were measured by the stack foil technique in the 3He energy range of 15-45 MeV. The results were compared to the data from the TENDL-2019 library. Using the experimental excitation functions, the thick target yields of medically relevant rhenium radioisotopes were calculated.

[Revascularization or conservative strategy in patients with stable coronary heart disease: a contemporary view].

Choice between revascularization and conservative strategy in patients with stable coronary heart disease (CHD) is an important clinical problem, especially when the need for revascularization is not urged by severe ischemic symptoms. Revascularization aimed to improve prognosis is most justified in patients having high risk, based both on results of coronary angiography and functional tests. In the opinion of many experts, the high-risk features at stress-test is a key to identify patients in whom revascularization is most required among persons with high-risk coronary anatomy, as well as to select candidates for invasive treatment among patients with more favorable variants of coronary lesions. The advantage of revascularization over conservative treatment was demonstrated primarily in relation to coronary bypass surgery; however, the prospect of replacing surgery by an interventional treatment for prognostic reasons is extremely attractive. Although comparison of prognostic efficiency of percutaneous coronary intervention (PCI) and coronary bypass surgery (CABG) for some categories of patients with stable ischemic heart disease has yielded encouraging results, improved survival when using the PCI in direct comparison with optimal medical therapy was not convincingly confirmed to date. Implementation of PCI to improve prognosis in stable ischemic heart disease is still limited by a rather narrow range of indications and the relief of symptoms of ischemia remains its main purpose.

[Prediction of left ventricular remodeling after acute myocardial infarction].

Prediction of adverse left ventricular remodeling after acute myocardial infarction (AMI) may have important clinical implications. In this study, we evaluated the incidence of unfavorable changes of left ventricular volumes and ejection fraction after AMI. The ability of several cardiac markers, electrocardiographic and echocardiographic (including tissue Doppler) variables to predict adverse remodeling was demonstrated. The prognostic algorithm based on the investigated variables may help improve the treatment of patients after AMI.

Prediction of postinfarction remodeling of the left ventricle from parameters of tissue Doppler echocardiography.

The possibility of predicting undesirable postinfarction remodeling of the left ventricle from parameters of tissue doppler echocardiography was evaluated in 55 patients with a history of acute myocardial infarction. Low diastolic rates of normal segments and the absence of the peak of isovolumetric contraction in the dysfunction zone were the most significant predictors of unfavorable remodeling.

[Advanced age as a risk factor for heart failure after acute myocardial infarction].

Heart failure (HF) is one of the most unfavorable consequences of the acute myocardial infarction (AMI), resulting in increased hospitalization level and mortality. The patients of advanced age constitute the major part among patients with HF due to AMI. In 123 patients a number of variables of the acute phase were investigated as potential predictors of developing HF within 12 months after AMI and the role of age was assessed. The relation of HF, echocardiographic variables measured 12 months after infarction and age was also studied. On completion a one-year follow-up, 54 patients (44%) developed HF, mainly of 2nd NYHA class. The age of the patients was the only independent predictor of HF among the variables of the acute phase (OR = 1.06 under 95% CI (1.01-1.12). The age over 65 years demonstrated 78% sensitivity and specificity in predicting development of HF. Among parameters estimated at the end of 12-months follow-up, age (OR = 0.934 under 95% CI (0.889-0.983) and echocardiographic wall motion score index (WMSI) (OR = 0.031 under 95% CI (0.003-0.333) independently influenced the presence of HF The factor of age had decisive importance for HF development in group of the patients with medium infarct size. At WMSI range 1.6-1.89, 11 of 20 patients younger than 65 had no HF, whereas 8 of 9 patients older than 65 developed HF (p < 0.05). Thus, age is a major independent predictor of development of HF within the first year after AMI. The patients of the senior age group 65+) have a high risk of HF with medium infarct size, which does not result in HF in patients of younger age.

[The effect of thymic peptides on the development of streptozotocin-induced diabetes mellitus]. / Vliianie peptidov timusa na razvitie streptozototsinindutsirovannogo sakharnogo diabeta.

Streptosotocin was administered to 21 test animals and 19 control ones. Preventively, the former were given T-activin, the latter--saline. 73% of the test animals were free of hyperglycemia, insulinopenia, activation of lipid peroxidation, morphologic evidence of beta-cell damage. In control animals diabetes mellitus arose in 84% manifesting with marked hyperglycemia, insulinopenia, LPO activation, morphological signs of beta-cell damage, lymphocytic infiltration of the islets. From the results obtained it can be concluded that T-activin has a prominent protective effect against diabetes mellitus (chi-square = 6.34, p < 0.05) which can be explained by its antioxidant and immunotropic activity.

[The immunoadjuvant properties of hydroxyapatite with ultrahigh dispersity]. / Issledovaniue immunoad''iuvantnykh svoistv gidroksiapatita ul'travysokoi dispersnosti.

Chemically pure hydroxyapatite (HA) with particles less than 140 microns, less than 60 microns, and 0.01 to 0.03 microns was studied. The immunoadjuvant properties were assessed from the count of IgM-secreting cells and titer of IgG antibodies. Mice were immunized with Salmonella Vi antigen, using mixtures of the antigen with HA with different size of particles. Preparations with particles less than 60 microns and 0.01 to 0.03 micron had a reliable immunoadjuvant effect, whereas HA with particles of up to 140 microns in size did not show such an effect; these data are in line with those published elsewhere about HA as a surfactant. At the same time, our findings give grounds to speak about new prospects of HA use as a carrier of immunocorrective properties.

[Enhancement of infection resistance of mice infected with Salmonella typhi by factors of immune lymph nodes]. / Povyshenie protivoinfektsionnoi rezistentnosti myshei, zarazhennykh Salmonella typhi, faktorami immunnykh limfaticheskikh uzlov.

Mediators, secreted by lymph node cells shortly after immunization and draining the site of the injection of the antigen, produced a nonspecific activating effect on cells of the macrophagal series. The preventive injection of immune lymph node factors induced an increase in nonspecific resistance to S. typhi TU2 [correction of Ty2] No. [correction of N]4446.

[Effects of immune lymph node factors on formation of immunological memory]. / Vliianie faktorov immunykh limfaticheskikh uzlov na formirovanie immunologicheskoi pamiati.

Two various fractions have been formed on the sephadex G-200 from culture supernatants of the lymph nodes cells isolated in 6h after immunization of animals by various antigens. The first fraction possessed the main biological properties peculiar to the earlier described factor of the immune lymph nodes (FILN), intensified proliferation of cells of the popliteal lymph nodes and increased the killer activity of peritoneal lymphocytes. Introduction of FILN simultaneously with ram erythrocytes led to more than a five-fold increase of humoral immune response.

[The nature of the factors in immune lymph nodes that stimulate humoral and cellular immune reactions]. / Priroda fakotorv immunnykh limfaticheskikh uzlov, stimuliruiushchikh gumoral'nye i kletochnye immunnye reaktsii.

In the early period after antigen action, cells of the lymph node draining area of antigen injection produce a factor, which after its administration to intact mice, promotes intensified migration of myelopeptide producers in the bone marrow and increases bone marrow suppressor activity. Factor administration produced 2-3-fold increase in macrophage, peritoneal and lymph node count as compared with control, and 2-4-fold increase in humoral and cellular immune response. The factor consists of three easily identifiable components: Ig, MHC class II determinants and antigen determinants, that form unique complex similar to, or identical with the complexes detected in vivo within 3-6 hours after immunization in serum by other authors.

[The clinical significance of the audible and mechanographic manifestations of mitral valve prolapse]. / Klinicheskoe znachenie zvukovykh i mekhanograficheskikh proiavlenii prolapsa mitral'nogo klapana.

Graphic techniques were employed to examine 82 patients with mitral valve prolapse verified on echocardiography. In addition to the known acoustic symptoms, enhancement of tones III, IV and V was identified, especially in transmitral regurgitation, together with inverted alternating of the components of tones I and II. Mitral click (OS) was discovered in one third of the examined. Uninterrupted protodiastolic and presystolic murmurs were found more seldom. They were more well-defined on the phonocardiogram recorded from the esophagus, at the level of the mitral valve. The right and left ventricular apex cardiography made it possible to diagnose hyperdynamia of the left atrium, the shortening of isometric relaxation of the left ventricle on elongation of this phase of the right ventricle. Both the curves had the M-like deformation in the systole. On the apex cardiogram of the left ventricle, the O point was always low, and the OF amplitude (rapid ventricular filling) was increased. During regurgitation, the OF transformed to an anomalous positive wave (a "surge"). Simultaneous alterations in the jugular phlebogram and in both apex cardiograms reflect changes in all four heart chambers. In part of the examined, pulmonary hypertension was established with the aid of indirect techniques. Esophagoatriography turned out diagnostically instrumental, since in some of the patients it enabled identification of systolic expansion of the entire posterior wall of the left atrium (regurgitation).

[Expert evaluation of medical documentation data in estimating the severity of injuries]. / Ob ekspertnoi otsenke dannykh v meditsinskoi dokumentatsii pri ystanolenii stepeni tiazhesti telesnykh povrezhdenii.

Analysis of false expert conclusions related to unjustified clinical diagnosis is given. Failure of critical attitude of medicolegal experts to X-ray and neurologic symptomatology data in posttraumatic period is stressed.

[Shape of the left ventricular cavity during ejection in patients with ischemic heart disease]. / Forma polosti levogo zheludochka v period izgnaniia u bol'nykh ishemicheskoi bolezn'iu serdtsa.

Different types of left-ventricular wall movement were demonstrated in normal subjects and coronary patients, the differences being due to different degrees of reduction in the equatorial diameter of the cavity in the ejection phase. Rationale are given for using the mean diameter for left-ventricular volume calculations. A linear relationship has been demonstrated between the degree of diameter reduction and the ejection fraction. The latter is shown to be dependent on left-ventricular end diastolic volume. Regional myocardial contractility, a parameter of high diagnostic value, based on segmental ejection fraction, is introduced.

[Study of the glucocorticoid function of the adrenals in patients with diabetes mellitus using a minor dexamethasone test]. / Issledovanie gliukokortikoidnoi funktsii nadpochechnikov u bol'nykh sakharnym diabetom s pomoshch'iu malogo deksametazonovogo testa.

The purpose of the paper is to define the state of glucocorticoid function in 37 male and female patients with types I and II diabetes mellitus of various degree of compensation before and after dexamethasone blockade of the hypothalamohypophyseoadrenal system (0.5 mg 4 times for 2 days). The level of cortisol in the plasma was determined by a radioimmunoassay using Sorin kits. Statistical data processing was performed using the d-3-28 computer. In patients with types I and II diabetes mellitus at the stage of compensation the level of plasma cortisol did not differ from that of persons without diabetes mellitus; in decompensation of types I and II diabetes mellitus its considerable increase was noted. After the dexamethasone test the more pronounced was a degree of decompensation of diabetes mellitus, the higher was the level of cortisol, i.e. there was resistance to dexamethasone inhibiting action, especially in type I which could be accounted for by deeper metabolic derangements in this type of diabetes mellitus and an increase in the threshold of sensitivity of the hypothalamic centers to dexamethasone. Therefore the minor dexamethasone test could be used for determination of a degree of metabolic compensation of patients with diabetes mellitus.

[Evolution of the shape of the left ventricular cavity at different phases of the cardiac cycle in healthy persons and ischemic heart disease patients]. / Evoliutsiia formy polosti levogo zheludochka v razlichnye fazy serdechnogo tsikla u zdorovykh lits i bol'nykh ishemicheskoi bolezn'iu serdtsa.

Cineventriculo- and echocardiographic studies of left-ventricular cavity demonstrated an increase in the deep diameter and the thinning and outward displacement of the posterior wall during the isovolumic systole in normal subjects. This change of shape was however uncommon and, if present, less pronounced in 19 patients with marked coronary heart disease (CHD). In normal subjects, posterior wall movement amplitude was always greater than that of the anterior wall, whereas in coronary patients left-ventricular wall movement amplitudes were always similar. It is assumed that the lateral posterior wall displacement is due to a later myocardial activation in this area, while the absence of such movements is attributed to increased volume of ventricular cavity. The ratio of left-ventricular diameter to posterior wall thickness was actually below 3 in all normal subjects and above 3 in most of the coronary patients.

[Heart rhythm disorders in mitral valve prolapse syndrome and their treatment]. / Narusheniia serdechnogo ritma pri sindrome prolapsa mitral'nogo klapana i ikh lechenie.

Sixty-three patients with the mitral prolapse (MP) syndrome and a variety of heart rhythm disorders were studied. Diagnostic signs of MP and arrhythmias associated with this conditions are discussed. The most common heart rhythm and conductivity disorders encountered were ventricular extrasystoles (in 27 patients) and paroxysmal atrial fibrillation (in 13). The mechanisms of cardiac arrhythmias and blocks, and principles of their treatment in patients with the MP syndrome are discussed.