Development of 225Ac/213Bi generator based on α-ZrP-PAN composite for targeted alpha therapy.

BACKGROUND: Radioligand therapy using alpha emitters has gained more and more prominence in the last decade. Despite continued efforts to identify new appropriate radionuclides, the combination of 225Ac/213Bi remains among the most promising. Bismuth-213 has been employed in clinical trials in combination with appropriate vectors to treat patients with various forms of cancer, such as leukaemia, bladder cancer, neuroendocrine tumours, melanomas, gliomas, or lymphomas. However, the half-life of 213Bi (T½ = 46 min) implies that its availability for clinical use is limited to hospitals possessing a 225Ac/213Bi radionuclide generator, which is still predominantly scarce. We investigated a new Ac/Bi generator system based on using the composite sorbent α-ZrP-PAN (zirconium(IV) phosphate as active component and polyacrylonitrile as matrix). The developed 225Ac/213Bi generator was subjected to long-term testing after its development. The elution profile was determined and the elution yield, the contamination of the eluate with the parent 225Ac and the contamination of the eluate with the column material were monitored over time. RESULTS: The high activity (75 MBq of parent 225Ac) generator with a length of 75 mm and a diameter of 4 mm containing the composite sorbent α-ZrP-PAN with a particle size of 0.8 to 1.0 mm as the stationary phase, eluted with a mixture of 10 mM DTPA in 5 mM nitric acid, provided 213Bi with yields ranging from 77 % to 96 % in 2.8 mL of eluate, with parent 225Ac contamination in the order of 10-3 %, up to twenty days of use. CONCLUSION: All the results of the monitored parameters indicate that the composite sorbent α-ZrP-PAN based separation system for the elution of 213Bi is a very promising and functional solution.

α-Zirconium(IV) Phosphate: Static Study of 225Ac Sorption in an Acidic Environment and Its Kinetic Sorption Study Using natEu as a Model System for 225Ac.

Zirconium phosphate (ZrP), especially its alpha allotropic modification, appears to be a very promising sorbent material for the sorption and separation of various radionuclides due to its properties such as an extremely high ion exchange capacity and good radiation stability. Actinium-225 and its daughter nuclide 213Bi are alpha emitting radioisotopes of high interest for application in targeted alpha therapy of cancer. Thus, the main aim of this paper is to study the sorption of 225Ac on the α-ZrP surface and its kinetics, while the kinetics of the sorption is studied using natEu as a non-radioactive homologue of 225Ac. The sorption properties of α-ZrP were tested in an acidic environment (hydrochloric and nitric acid) using batch sorption experiments and characterized using equilibrium weight distribution coefficients Dw (mL/g). The modeling of the experimental data shows that the kinetics of 225Ac sorption on the surface of α-ZrP can be described using a film diffusion model (FD). The equilibrium weight distribution coefficient Dw for 225Ac in both hydrochloric and nitric acid reached the highest values in the concentration range 5.0-7.5 mM (14,303 ± 153 and 65,272 ± 612 mL/g, respectively). Considering the results obtained in radioactive static sorption experiments with 225Ac and in non-radioactive kinetic experiments with natEu, α-ZrP seems to be a very promising material for further construction of a 225Ac/213Bi generator.

Preparation and Surface Characterization of Cerium Dioxide for Separation of 68Ge/68Ga and Other Medicinal Radionuclides.

The overall need for the preparation of new medicinal radionuclides has led to the fast development of new sorption materials, extraction agents, and separation methods. Inorganic ion exchangers, mainly hydrous oxides, are the most widely used materials for the separation of medicinal radionuclides. One of the materials that has been studied for a long time is cerium dioxide, a competitive sorption material for the broadly used titanium dioxide. In this study, cerium dioxide was prepared through calcination of ceric nitrate and fully characterized using X-ray powder diffraction (XRPD), infrared spectrometry (FT-IR), scanning and transmission electron microscopy (SEM and TEM), thermogravimetric and differential thermal analysis (TG and DTA), dynamic light scattering (DLS), and analysis of surface area. In order to estimate the sorption mechanism and capacity of the prepared material, characterization of surface functional groups was carried out using acid-base titration and mathematical modeling. Subsequently, the sorption capacity of the prepared material for germanium was measured. It can be stated that the prepared material is prone to exchange anionic species in a wider range of pH than titanium dioxide. This characteristic makes the material superior as a matrix in 68Ge/68Ga radionuclide generators, and its suitability should be further studied in batch, kinetic, and column experiments.

Removal of manganese by adsorption onto newly synthesized TiO2-based adsorbent during drinking water treatment.

Manganese is naturally present in water, but its increased concentration in potable water is undesirable for multiple reasons. This study investigates an alternative method of demanganization by a newly synthesized TiO2-based adsorbent prepared through the transformation of titanyl sulphate monohydrate to amorphous sodium titanate. Its adsorption capacity for Mn2+ was determined, while a range of influential factors, such as the effect of contact time, adsorbent dosage, pH value, and added ions was evaluated. The adsorbent appeared highly effective for Mn2+ removal owing to its unique characteristics. Besides adsorption via electrostatic interactions, ion-exchange was also involved in the Mn2+ removal. Although the Mn2+ removal occurred within the whole investigated pH range of 4-8, the maximum was achieved at pH 7, with qe = 73.83 mg g-1. Equilibrium data revealed a good correlation with Langmuir isotherm in the absence of any ions or in the presence of monovalent co-existing ions, while the results in the presence of divalent co-existing ions showed a better fit to Freundlich isotherm. Additionally, the presence of monovalent cations (Na+, K+) only slightly decreased the Mn2+ removal efficiency as compared to divalent cations (Ca2+, Mg2+) that caused a greater decrease; however, the effect of anions (Cl-, SO42-) was insignificant. To provide insight into the adsorbent safety, the toxicity assessment was performed and showed no harmful effect on cell activity. Furthermore, the residual concentration of titanium after adsorption was always below the detection limit. The results imply that the synthesized TiO2-based adsorbent is a safe promising alternative method for demanganization.Highlights The synthesis of amorphous TiO2-based adsorbent was presented.The TiO2-based adsorbent was found to be efficient for Mn2+ removal.The Mn2+ removal mechanisms were adsorption and ion-exchange.Increasing pH enhanced the efficiency of Mn2+ removal.Divalent cations decreased the Mn2+ removal efficiency more than monovalent cations.

Continuous long-term monitoring of leaching from microplastics into ambient water - A multi-endpoint approach.

Widespread pollution of aquatic environments by microplastics (MPs) is a serious environmental threat. Despite the knowledge of their occurrence and properties rapidly evolving, the potential leaching from MPs remains largely unexplored. In this study, 16 different types of MPs prepared from consumer products were kept in long-term contact with water, while the leachates were continuously analysed. Most of the MPs released significant amounts of dissolved organic carbon, up to approximately 65 mg per g MPs after 12 weeks of leaching, and some MPs also released dissolved inorganic carbon. Other elements identified in the leachates were Al, Ba, Ca, Fe, K, Mg, Mn, Na, Si, and Zn. Of those, Ca, K, and Na were detected most frequently, while Ca reached the highest amounts (up to almost 2.5 mg per g MPs). Additionally, 80 organic individuals were tentatively identified in the leachates, mostly esters, alcohols, and carboxylic acids. Some compounds considered harmful to human health and/or the environment were detected, e.g., bisphenol A or phthalate esters. The current results provide insight into the transfer of various compounds from MPs to ambient water, which might have consequences on the fluxes of carbon and metals, as well as of specific organic contaminants.

Investigating adsorption of model low-MW AOM components onto different types of activated carbon - influence of temperature and pH value.

Low molecular weight algal organic matter (AOM), as a frequent water contaminant with poor coagulation efficiency, adversely affects the quality of produced water and serves as a source of potentially carcinogenic disinfection by-products. AOM removal from water is inevitable to eliminate the negative health and environmental impacts. This research evaluates the removal of arginine, phenylalanine and aspartic acid, which are amino acids abundant in AOM. Adsorption experiments were performed at 10, 18 and 25 °C and pH 5, 7 and 9 using two different activated carbons (FTL, PIC). Amino acids showed endothermic adsorption behaviour, with a higher removal at higher temperature. Higher temperature increased the diffusion of amino acid molecules, reduced the solution viscosity, or enhanced the hydrophobic interactions contributing to adsorption. The effect of temperature manifested differently during experiments depending on the chemical nature of the amino acids, the pH value and the surface properties of the carbon. Phenylalanine isotherms showed specific waves (Langmuir type 4). pH had a greater effect on arginine adsorption than did temperature. Aspartic acid isotherms exhibited a decrease in adsorption at higher pH values and higher temperatures. The principal mechanisms involved in amino acid adsorption were hydrophobic interactions, electrostatic interactions or hydrogen bonds.

Current knowledge in the field of algal organic matter adsorption onto activated carbon in drinking water treatment.

The increasing occurrence of algal and cyanobacterial blooms and the related formation of algal organic matter (AOM) is a worldwide issue that endangers the quality of freshwater sources and affects water treatment processes. The associated problems involve the production of toxins or taste and odor compounds, increasing coagulant demand, inhibition of removal of other polluting compounds, and in many cases, AOM acts as a precursor of disinfection by-products. Previous research has shown that for sufficient AOM removal, the conventional drinking water treatment based on coagulation/flocculation must be often accompanied by additional polishing technologies such as adsorption onto activated carbon (AC). This state-of-the-art review is intended to serve as a summary of the most current research on the adsorption of AOM onto AC concerning drinking water treatment. It summarizes emerging trends in this field with an emphasis on the type of AOM compounds removed and on the adsorption mechanisms and influencing factors involved. Additionally, also the principles of competitive adsorption of AOM and other organic pollutants are elaborated. Further, this paper also synthesizes previous knowledge on combining AC adsorption with other treatment techniques for enhanced AOM removal in order to provide a practical resource for researchers, water treatment plant operators and engineers. Finally, research gaps regarding the AOM adsorption onto AC are identified, including, e.g., adsorption of AOM residuals recalcitrant to coagulation/flocculation, suitability of pre-oxidation of AOM prior to the AC adsorption, relationships between the solution properties and AOM adsorption behaviour, or AOM as a cause of competitive adsorption. Also, focus should be laid on continuous flow column experiments using water with multi-component composition, because these would greatly contribute to transferring the theoretical knowledge to practice.

Di-4-ANEPPS Modulates Electrical Activity and Progress of Myocardial Ischemia in Rabbit Isolated Heart.

AIMS: Although voltage-sensitive dye di-4-ANEPPS is a common tool for mapping cardiac electrical activity, reported effects on electrophysiological parameters are rather. The main goals of the study were to reveal effects of the dye on rabbit isolated heart and to verify, whether rabbit isolated heart stained with di-4-ANEPPS is a suitable tool for myocardial ischemia investigation. METHODS AND RESULTS: Study involved experiments on stained (n = 9) and non-stained (n = 11) Langendorff perfused rabbit isolated hearts. Electrophysiological effects of the dye were evaluated by analysis of various electrogram (EG) parameters using common paired and unpaired statistical tests. It was shown that staining the hearts with di-4-ANEPPS leads to only short-term sporadic prolongation of impulse conduction through atria and atrioventricular node. On the other hand, significant irreversible slowing of heart rate and ventricular conduction were found in stained hearts as compared to controls. In patch clamp experiments, significant inhibition of sodium current density was observed in differentiated NG108-15 cells stained by the dye. Although no significant differences in mean number of ventricular premature beats were found between the stained and the non-stained hearts in ischemia as well as in reperfusion, all abovementioned results indicate increased arrhythmogenicity. In isolated hearts during ischemia, prominent ischemic patterns appeared in the stained hearts with 3-4 min delay as compared to the non-stained ones. Moreover, the ischemic changes did not achieve the same magnitude as in controls even after 10 min of ischemia. It resulted in poor performance of ischemia detection by proposed EG parameters, as was quantified by receiver operating characteristics analysis. CONCLUSION: Our results demonstrate significant direct irreversible effect of di-4-ANEPPS on spontaneous heart rate and ventricular impulse conduction in rabbit isolated heart model. Particularly, this should be considered when di-4-ANEPPS is used in ischemia studies in rabbit. Delayed attenuated response of such hearts to ischemia might lead to misinterpretation of obtained results.

Haloperidol increases expression of the inositol 1,4,5-trisphosphate receptors in rat cardiac atria, but not in ventricles.

Numerous ligands of sigma receptors are known to prolong the QT interval and therefore cause a variety of arrhythmias. High affinity binding sites for the prototypical sigma ligand haloperidol were found in membranes of cardiac myocytes from adult rats. Activation of sigma 1 receptor leads to a release of calcium from the endoplasmic reticulum that follows increased synthesis of inositol 1,4,5-trisphosphate (IP3). We studied the effect of long-term haloperidol treatment on the expression of sigma 1 receptors, IP3 receptors of type 1 and 2 in the individual parts of the rat heart, in isolated rat cardiomyocytes and in PC12 cells. We have found that prolonged treatment with haloperidol significantly increased mRNA levels of sigma 1 receptors in both atria and ventricles. Sigma 1 receptor's mRNA was increased also in isolated cardiomyocytes. Haloperidol treatment affects the expression of IP3 receptors of type 1 and 2 in cardiac atria, but not in cardiac ventricles. We observed increase in IP3 receptors in differentiated PC12 cells, but not in isolated cardiomyocytes. We propose that this increase might participate in triggering cardiac arrhythmias during haloperidol treatment, which has to be further verified.

Apparent desensitization of the effects of sigma receptor ligand haloperidol in isolated rat and guinea pig hearts after chronic treatment.

The supposed role of cardiac sigma receptors is fine tuning of contractility. Sigma receptors affect several ionic channels and hence their signaling is reflected by the electrophysiological properties of the heart. Numerous ligands of sigma receptors are known to prolong the QT interval and therefore cause a variety of arrhythmias, including severe ones. The effects of the prototypical sigma ligand haloperidol have been studied extensively in humans as well as in various animal models, primarily after acute administration. We examined the incidence of arrhythmias, changes in heart rate, and prolongation of QT interval in isolated Langendorff-perfused rat and guinea pig hearts after they were exposed to nanomolar concentrations of haloperidol. Hearts from both untreated (acute) and pretreated (chronic) animals were investigated. While QT prolongation and arrhythmias due to haloperidol administration were observed in untreated rat and guinea pig hearts, arrhythmias were completely prevented in both species of chronically treated animals. In treated guinea pigs, the results were generally less convincing. Since the hearts were exposed to nanomolar concentration of haloperidol, we conclude that our data may be explained by desensitization of sigma receptors.