Diagnostic value of [99mTc]Tc-PSMA-I&S-SPECT/CT for the primary staging and restaging of prostate cancer.

Background: A large number of studies have proved that prostate-specific membrane antigen-positron emission tomography/computer tomography (PSMA-PET/CT) provides excellent accuracy in primary staging and restaging of prostate cancer. Less data exist with PSMA-single photon emission computed tomography (SPECT)/CT investigations. Objective: The aim of this study was to evaluate the performance of [99mTc]Tc-PSMA-I&S (for imaging and surgery) in prostate cancer. Design and methods: We retrospectively analysed PSMA-SPECT/CT scans of 20 healthy volunteers and 100 male patients with prostate cancer. All of them had histologically confirmed prostate cancer. In all, 28 patients were examined for primary staging and 72 for biochemical recurrence or progressive disease. Whole body SPECT/CT imaging was carried out 6 h after the intravenous administration of 666 ± 102 MBq [99mTc]Tc-PSMA-I&S. Images were evaluated visually and semi-quantitatively. Results: Patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy for primary prostate cancer were 86%, 100%, 100%, 83% and 92%, respectively. For detecting metastases in primary staging, these values were 88%, 100%, 100%, 85% and 93%, respectively. The radiopharmaceutical uptake of primary prostate cancer was significantly higher than in normal prostate. The patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the method in the visualization of local recurrence were 67%, 100%, 100%, 86% and 89%, and for detecting metastases in restaging were 91%, 92%, 98%, 75% and 91%, respectively. In restaging, detection rates were 37% under prostate-specific antigen level of 1 ng/mL, 74% between 1 and 5 ng/mL and 80% >5 ng/mL. Conclusion: [99mTc]Tc-PSMA-I&S-SPECT/CT can be easily integrated into the routine diagnostic practice, and it provides usable data in primary staging and restaging of prostate cancer. Quantitative assessment of PSMA-SPECT/CT has the potential to be used to differentiate between physiological and pathological intraprostatic tracer uptake.

A comparative experimental investigation of dynamic viscosity of ZrO2/DW and SiC/DW nanofluids: Characterization, rheological behavior, and development of new correlation.

In general, A nanofluid is a substance in which solids and fluids are mixed. The nano-powder of zirconium oxide (ZrO2) and silicon carbide (SiC) was dispersed into the distilled water (DW) using the widely adopted two-step technique. A Brookfield viscometer was used to measure the viscosity of the nanoparticles of ZrO2/DW and SiC/DW, where the temperature ranged between 20 and 60 °C and different solid volume fractions of 0.025, 0.05, 0.075, and 0.1 % were used. An examination of the mono nanofluids of ZrO2/DW and SiC/DW was conducted to assess their rheological behaviour. The findings of the experiments revealed that the Newtonian behaviour did not change when the nano-powder was added. Increasing the solid volume fraction of the nanoparticles and lowering the temperature resulted in the sample's dynamic viscosity being augmented. Hence, as the temperature rose, nanoparticles had a more observable impact on the viscosity. Furthermore, the findings showed that the increase in the ZrO2/DW nanofluid's viscosity peaked at 226.3 %, whereas for the SiC/DW nanofluid, it was 110.5 %. Additionally, according to the results of the experiments, new correlations capable of predicting the investigated nanofluids' viscosity in relation to solid concentration and temperature has been suggested. The study's results could motivate expanded utilization of nanofluids by researchers working on energy applications.

Prostate-specific membrane antigen-based imaging for stereotactic irradiation of low-volume progressive prostate cancer: a single-center experience.

Introduction: Prostate-specific membrane antigen (PSMA) is a transmembrane protein that may be expressed on the surface of prostate cancer (PC) cells. It enables a more sensitive and specific diagnosis PC, compared to conventional anatomical imaging. Aim: The integration of PSMA-based imaging in the personalized radiotherapy of PC patients and the evaluation of its impact on target volume definition if stereotactic body radiotherapy (SBRT) is planned for locally recurrent or oligometastatic disease. Patients and methods: The data from 363 examinations were analyzed retrospectively. Inclusion criteria were histologically verified PC and clinical data suggesting local recurrence or distant metastasis. Whole-body 99mTc-PSMA-I&S single-photon emission computed tomography (SPECT)/CT or 18F-JK-PSMA-7 positron emission tomography/computer tomography (PET/CT) was carried out, and the evaluation of the scans and biological tumor volume contouring was performed at the Department of Nuclear Medicine. The target volume delineation on topometric CT (TCT) scan was performed at the Department of Oncotherapy. The comparison of the two volumes was performed by image fusion and registration. Results: From 363 PSMA isotope-based examinations, 84 lesions of 64 patients were treated with SBRT. In 50 patients, 70 lesions were examined for intermodality comparison. The target volume defined by the PSMA density was significantly smaller than the tumor size defined by the TCT scan: GTVCT (gross tumor volume on the TCT), 27.58 ± 46.07 cm3; BTVPSMA (biological target volume on the PSMA-based examination), 16.14 ± 29.87 cm3. During geometrical analyses, the Dice similarity coefficient (DSC) was 0.56 ± 0.20 (0.07-0.85). Prostate-specific antigen (PSA) control was performed to evaluate the response: mean pre-radiotherapy (pre-RT) PSA was 16.98 ng/ml ( ± SD: 33.81), and post-RT PSA at 3 months after SBRT was 11.19 ng/ml ( ± SD: 32.85). Three-month post-therapy PSMA-based imaging was performed in 14 cases, in which we observed a decrease or cessation of isotope uptake. Conventional imaging control was performed in 42 cases (65.6% of all cases): 22 (52.4%) complete remissions, 14 (33.3%) partial remissions, four (9.5%) stable diseases, and two (4.8%) progressive diseases were described. Conclusion: PSMA-based imaging is a promising diagnostic method for specifying the stage and detecting the low-volume progression. Our results suggest that PSMA-based hybrid imaging can influence treatment decisions and target volume delineation for SBRT.

The effects of expected and unexpected stress on inappropriate aggression in simulated police interventions.

Here we performed a before-after ABA-design study in police cadets (N = 82) to compare the effects of unexpected (event-triggered) and expected (anticipatory) stressors on aggression. On the first day of the study, participants filled in the Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale (BIS) and were fitted with heart rate (HR) monitors, which remained attached till the end of the study. On day 2, they were instructed to perform a police intervention in a realistic training environment. The intervention was preceded either by a warning or by a reassuring audio recording that forecasted violent or routine interventions, respectively. Both groups encountered hostile suspects at the intervention site, the behavior of which, however, did not justify the use of force e.g., aggression. The warning resulted in a gradually developing anticipatory stress as shown by HRs. Cadets exposed to the reassuring audio recording showed minimal anticipatory stress but responded to the hostile suspects by an abrupt increase in HRs, which was missing in the warned group. The magnitude of HR responses was similar in the two groups, only their temporal evolution differed. Although aggression showed some associations with BPAQ and BIS scores, the main predictors of behavior were HR changes according to a Multiple Regression analysis. The gradually developing anticipatory stress was associated with low, whereas the abrupt increase in HRs was associated with high aggression. Our findings suggest that the anticipation of a stressful event improves behavioral control whereas an unexpected stress strongly promotes aggression.

A bibliometric analysis of the application of solar energy to the organic Rankine cycle.

Solar Thermal is one of many heat sources that support the organic Rankine cycle (ORC) system. The advantage of using solar thermal as a heat source when combined with the ORC system is that it can provide affordable energy supplies in remote areas and it is suitable in disaster territories. Growth in solar-ORC research is not only on a lab/workshop scale but also on an industrial scale. Most articles refer to methods and tools in the design process, combining heat and improvement of the cycle, working fluids selection, and case studies based on primary or secondary data. The paper reports the newest trends on the research of solar application on ORC using bibliometric analysis. The study of bibliometric using VOSviewer was recognized as a captivating method in the literature that allows examining the scientific progress of a particular topic. Moreover, a qualitative approach can be performed by analyzing the keywords contained in different documents to identify a circumstance that features the research trend and to understand future viewpoints.

Comparison of the Cardiovascular Effects of Extreme Psychological and Physical Stress Tests in Male Soccer Players.

BACKGROUND: The purpose of our study was to compare the physiological effects of extreme physical and psychological stress tests in male soccer players, since these two types of stress apply to athletes with high performance requirements. METHODS: A total of 63 healthy male soccer players participated in this study, all of whom underwent both of the tests. A physical stress test was carried out in an exercise physiology laboratory, where subjects completed an incremental treadmill running test to full exhaustion, and a psychological test was performed in a military tactical room, where subjects met a street offence situation. Heart rate variability (HRV) and blood pressure (BP) were recorded directly before, immediately after, and 30 min after the stress tests. RESULTS: The majority of HRV indices changed significantly in both stress protocols. Inverse, significant changes (positive for the physical test, negative for the psychological test, p < 0.001) were found when comparing the alterations of HRV indices between the tests. Significant differences were found in the changes in systolic (p = 0.003) and diastolic (p < 0.001) BP between the test protocols, and also between the baseline and post-test measurements (p < 0.001). CONCLUSION: Both HRV and BP are sensitive physiological parameters to measure the impact of extreme physical and/or psychological stress.

Radiation Dosimetry of 99mTc-PSMA I&S: A Single-Center Prospective Study.

99mTc-PSMA I&S is a prostate-specific membrane antigen (PSMA) tracer that can be used for planar and SPECT/CT γ-imaging and radioguided surgery. The primary aim of this study was to estimate the dosimetry of 99mTc-PSMA I&S using a hybrid method (sequential γ-planar imaging and 1 single SPECT/CT) in healthy volunteers. The secondary aim was to depict the tracer biodistribution and tumor-to-background ratios (TBRs) in patients with prostate cancer (PCa). Methods: Dosimetry of 99mTc-PSMA I&S was investigated in 4 healthy volunteers. Whole-body planar imaging was acquired at 1, 2, 3, 6, and 24 h and SPECT/CT at 6 h after tracer injection. Contours of organs were drawn on all acquisitions to determine organ activity at each time point. Absorbed dose was estimated using 2 methods: independent curve-fitting manual method (Levenberg-Marquardt-based algorithm using dose factors from RAdiation Dose Assessment Resource [RADAR] website) and OLINDA/EXM software (version 2.0; HERMES Medical Solutions). Biodistribution of 99mTc-PSMA I&S was assessed in 10 patients with PCa on SPECT/CT images at 6 h. Tumor uptake (SUVmax), and TBR (tumor SUVmax/background organ SUVmean) using muscle (T/M), bladder (T/B), and intestine (T/I) as background organs were determined. Results: The mean injected activity of 99mTc-PSMA I&S was 717 MBq (range: 562-828 MBq). No adverse events related to the injection of 99mTc-PSMA I&S were reported. The average radiation effective dose was 0.0055 mSv/MBq with the RADAR manual method and 0.0052 mSv/MBq with OLINDA/EXM. Total body effective dose ranged between 3.33-4.42 and 3.11-4.23 mSv, respectively. All PCa patients showed high tracer uptake in primary and metastatic lesions with T/M, T/B, and T/I ranging from 5.29-110, 0.11-7.02, and 0.96-16.30, respectively. Conclusion: Effective doses of 99mTc-PSMA I&S were comparable to those known for most of the 99mTc tracers and was lower than for the 68Ga-labeled and 18F-labeled agents. 99mTc-PSMA I&S SPECT/CT showed high TBR in PCa patients. This study can provide required data for translation and approval of 99mTc-PSMA I&S by regulatory agencies.

[Theranostics in 2020: Neuroendocrine tumors]. / Teranosztikumok 2020-ban: Neuroendokrin tumorok.

This article presents the diagnostic and therapeutic nuclear medicine methods for neuroendocrine tumors in accordance with current guidelines. The paper begins with a general characterization of neuroendocrine tumors, followed by a broad introduction to laboratory and imaging diagnostic techniques, and a detailed discussion of peptide receptor radionuclide therapy and meta-iodobenzylguanidine treatment. Finally, the article provides an insight into current research and future developments.

[Initial experiences with 99mTc-PSMA-SPECT/CT in patients with prostate cancer]. / Kezdeti tapasztalatok a 99mTc-PSMA-SPECT/CT-vel prosztatarákos betegekben.

INTRODUCTION: The prostate-specific membrane antigen (PSMA) is a transmembrane protein, that is highly expressed on the surface of prostate cancer cells. In the last few years, several PSMA-specific ligands have been developed, that can be successfully used to detect primary prostate cancer, tumor recurrences and metastases as well. AIM: The goal of our work was to examine the clinical application of a 99mtechnetium-labeled PSMA-radiopharmaceutical as part of the routine diagnostics of prostate cancer. METHOD: We examined 15 male patients with verified prostate adenocarcinoma with suspicion of progression or recurrence of the disease. We performed whole-body PSMA-SPECT/CTs and multiparametric MRIs of the prostate and the pelvic regions within a week. We used 99mTc-mas3-y-nal-k(Sub-KuE) for the PSMA-SPECT scans. The images were visually evaluated by independent observers. The results were compared with the follow-up bone scintigraphies as well. RESULTS: Twenty-two PSMA-positive lesions were found. Nine of them were localized outside, 13 were within the MRI's field of view. From these 13 lesions, 7 matched with the SPECT/CT results and in 5 cases the MRI images showed no abnormalities. In one case, bone metastasis was suspected on the MRI scan but there was no corresponding pathological tracer uptake on the SPECT images. In two patients, none of the examinations showed signs of prostate malignancy. Four patients had PSMA-positive bone metastases. One of them had a matching PSMA/SPECT and bone scintigraphy result and in one case the PSMA examination showed metastasis in contrast to the negative bone scintigraphy. CONCLUSION: PSMA-SPECT/CT with 99mTc-mas3-y-nal-k(Sub-KuE) is a promising diagnostic tool. This technique is capable of visualizing bone metastases and it can detect local recurrences and visceral metastases as well. Orv Hetil. 2018; 159(35): 1433-1440.

Cardiac autonomic functions and the emergence of violence in a highly realistic model of social conflict in humans.

Among the multitude of factors that can transform human social interactions into violent conflicts, biological features received much attention in recent years as correlates of decision making and aggressiveness especially in critical situations. We present here a highly realistic new model of human aggression and violence, where genuine acts of aggression are readily performed and which at the same time allows the parallel recording of biological concomitants. Particularly, we studied police officers trained at the International Training Centre (Budapest, Hungary), who are prepared to perform operations under extreme conditions of stress. We found that aggressive arousal can transform a basically peaceful social encounter into a violent conflict. Autonomic recordings show that this change is accompanied by increased heart rates, which was associated earlier with reduced cognitive complexity of perceptions ("attentional myopia") and promotes a bias toward hostile attributions and aggression. We also observed reduced heart rate variability in violent subjects, which is believed to signal a poor functioning of prefrontal-subcortical inhibitory circuits and reduces self-control. Importantly, these autonomic particularities were observed already at the beginning of social encounters i.e., before aggressive acts were initiated, suggesting that individual characteristics of the stress-response define the way in which social pressure affects social behavior, particularly the way in which this develops into violence. Taken together, these findings suggest that cardiac autonomic functions are valuable external symptoms of internal motivational states and decision making processes, and raise the possibility that behavior under social pressure can be predicted by the individual characteristics of stress responsiveness.

Challenges in detecting magnesium stearate distribution in tablets.

Magnesium stearate (MS) is the most commonly used lubricant in pharmaceutical industry. During blending, MS particles form a thin layer on the surfaces of the excipient and drug particles prohibiting the bonding from forming between the particles. This hydrophobic layer decreases the tensile strength of tablets and prevents water from penetrating into the tablet restraining the disintegration and dissolution of the tablets. Although overlubrication of the powder mass during MS blending is a well-known problem, the lubricant distribution in tablets has traditionally been challenging to measure. There is currently no adequate analytical method to investigate this phenomenon. In this study, the distribution of MS in microcrystalline cellulose (MCC) tablets was investigated using three different blending scales. The crushing strength of the tablets was used as a secondary response, as its decrease is known to result from the overlubrication. In addition, coating of the MCC particles by MS in intact tablets was detected using Raman microscopic mapping. MS blending was more efficient in larger scales. Raman imaging was successfully applied to characterize MS distribution in MCC tablets despite low concentration of MS. The Raman method can provide highly valuable visual information about the proceeding of the MS blending process. However, the measuring set-up has to be carefully planned to establish reliable and reproducible results.

Investigation of drug distribution in tablets using surface enhanced Raman chemical imaging.

This paper reports the first application of surface enhanced Raman chemical imaging on pharmaceutical tablets containing the active ingredient (API) in very low concentrations. Taking advantage of the extremely intensive Raman signals in the presence of silver colloids, image aquisition time was radically decreased. Moreover, the investigation of drug distribution below the detection limit of regular micro-Raman spectrometry was made feasible. The characteristics of different manufacturing technologies could be revealed at very low API concentrations by using chemometric methods for processing and evaluating the large number of varying spectra provided with this imaging method.

Characterization of melt extruded and conventional Isoptin formulations using Raman chemical imaging and chemometrics.

Isoptin SR-E (Meltrex(®)) extruded tablets were assumed in a recent paper to be prepared with a composition different from a conventional (Isoptin SR) formulation. This study reveals, however, using Raman mapping and chemometric evaluation, that in fact the same composition, comprising Na alginate as polymer matrix, is used in both products. It means that only the difference in the manufacturing technology causes the reported sustained release of verapamil hydrochloride even in ethanol containing dissolution media. The products are compared based on the obtained Raman chemical images, which allowed concluding in a new structure-based explanation for the differences in the dissolution profiles in the presence of ethanol. It is also shown that extrusion technology influences the dissolution profile effectively, even in the cases when solid solution is formed only partially.

Characterization of drug-cyclodextrin formulations using Raman mapping and multivariate curve resolution.

Raman chemical imaging was used in the characterization of drug-excipient interactions between a drug and different types of cyclodextrins. Detailed analysis was carried out regarding the interactions between the active ingredient (API) and the cyclodextrins and the heterogeneity of the samples was studied using multivariate curve resolution-alternating least squares algorithm. The amount of recrystallized pure API was also estimated using the same curve resolution method. The Raman mapping results were validated via scanning electron microscopy-energy dispersive X-ray spectroscopy and X-ray powder diffraction. Raman mapping was found to be suitable to detect traces of pure crystalline API below the detection limit of X-ray powder diffraction.

Raman microscopic evaluation of technology dependent structural differences in tablets containing imipramine model drug.

Raman imaging method was used to characterize the effect of different manufacturing technologies on properties of the produced tablets, such as compound distribution, polymorphism, strength, and estimated active pharmaceutical ingredient (API) content. The obtained chemical maps were evaluated based on their visual appearance and on the statistical properties of the component scores obtained by direct classical least squares (DCLS) modelling. It is demonstrated that changes in the distribution of the API and excipients can be detected with chemical imaging and these differences are in close relationship with the applied granulation method and with the mechanical properties of the analyzed tablet. It is also shown that the chemical images used for characterizing the component distribution can also be processed for obtaining a cautious estimation to the mass fractions of the components.

[Biomechanics of intracranial aneurysms]. / Az aneurysmák biomechanikai tulajdonságai.

INTRODUCTION: Viscoelastic parameters of circumferential and meridional strips of ruptured and silent aneurysms were investigated (considered clinical and histological data either) in order to advance the prediction of risk of aneurysm rupture. METHOD: In our clinical practice, aneurysms managed by microsurgery aneurysm clipping were removed. Meridional and circumferential strips were cut. Strips were investigated by an uniaxial biomechanical instrument: distending force was recorded as the length of the strips was increased in steps. Normal stress-relaxation patterns were detected. The shape of strain curves well overlapped with the Standard Linear Solid Model curve, as had been expected. The viscosity, serial and parallel elastic moduli of the model were then computed. RESULTS: Linear correlation was demonstrated amongst peek distending force detected and aneurysm strip thickness. Steric inhomogeneity was detected at the meridional and circumferential strips. Strain-stress behaviour of ruptured and silent aneurysm specimen showed significant difference. Values of strips originated from patients suffered from hypertension as well as strips originated from aneurysms had been histologically found inflamed were higher. DISCUSSION: Results of these observations are going to be used to set three dimensional computer model in cooperation with IT team of Budapest University of Technology and Economics to advance rupture risk prediction.