Radionuclide therapy employing alpha emitters holds great potential for personalized cancer treatment. However, certain challenges remain when designing alpha radiopharmaceuticals, including the lack of stability of used radioconjugates due to nuclear decay events. In this work, ultrasmall silver telluride nanoparticles with a core diameter of 2.1 nm were prepared and radiolabeled with lead-212 using a chelator-free method with a radiolabeling efficiency of 75%. The results from the in vitro radiochemical stability assay indicated a very high retention of bismuth-212 despite the internal conversion effects originating from the decay of 212Pb. To further evaluate the potential of the nanoparticles, they were radiolabeled with indium-111, and their cell uptake and subcellular distribution were determined in 2D U87 cells, showing accumulation in the nucleus. Although not intentional, it was observed that the indium-111-radiolabeled nanoparticles induced efficient tumor cell killing, which was attributed to the Auger electrons emitted by indium-111. Combining the results obtained in this work with other favorable properties such as fast renal clearance and the possibility to attach targeting vectors on the surface of the nanoparticles, all well-known from the literature, these ultra-small silver telluride nanoparticles provide exciting opportunities for the design of theragnostic radiopharmaceuticals.@en

The relatively high linear energy transfer of Auger electrons, which can cause clustered DNA damage and hence efficient cell death, makes Auger emitters excellent candidates for attacking metastasized tumors. Moreover, gammas or positrons are usually emitted along with the Auger electrons, providing the possibility of theragnostic applications. Despite the promising properties of Auger electrons, only a few radiopharmaceuticals employing Auger emitters have been developed so far. This is most likely explained by the short ranges of these electrons, requiring the delivery of the Auger emitters to crucial cell parts such as the cell nucleus. In this work, we combined the Auger emitter ¹²⁵I and ultrasmall gold nanoparticles to prepare a novel radiopharmaceutical. The ¹²⁵I labeled gold nanoparticles were shown to accumulate at the cell nucleus, leading to a high tumor-killing efficiency in both 2D and 3D tumor cell models. The results from this work indicate that ultrasmall nanoparticles, which passively accumulate at the cell nucleus, have the potential to be applied in targeted radionuclide therapy. Even better tumor-killing efficiency can be expected if tumor-targeting moieties are conjugated to the nanoparticles.

@en

Two porphyrinic metal-organic frameworks (PCN-222 and PCN-224) were prepared and their potential as molybdenum adsorbents for the ⁹⁹Mo/^99mTc generator was explored. The molybdenum adsorption properties of the two adsorbents, including adsorption kinetics and equilibrium isotherms, were evaluated at different molybdenum concentrations and pH. The maximum adsorption capacity of PCN-222 and PCN-224 was evaluated to be 525 mg g⁻¹ and 455 mg g⁻¹, respectively. The possible adsorption mechanism was investigated by X-ray Photoelectron Spectra and Fourier-Transform Infrared Spectroscopy. The results demonstrated that molybdenum species were adsorbed on the two MOFs through electrostatic attraction and hydrogen bonds. In the case of PCN-222, the Mo-O-Zr coordination interaction also played an important role. Additionally, the elution performance of two ⁹⁹Mo/^99mTc generators developed by using PCN-222 and PCN-224 as adsorbents was measured to assess possible clinical applications. The PCN-222-based ⁹⁹Mo/^99mTc generator exhibited better elution performance and showed that around 56% of ^99mTc could be obtained without zirconium breakthrough when relatively high pH solutions were used (pH = 9.6).

@en

Four different MOFs were exposed to γrays by a cobalt-60 source reaching a maximum dose of 5 MGy. The results showed that the MIL-100 (Cr) and MIL-100 (Fe) did not exhibit obvious structural damage, suggesting their excellent radiation stability. MIL-101 (Cr) showed good radiation stability up to 4 MGy, but its structure started degrading with increasing radiation dose. Furthermore, the results showed that the structure of AlFu MOFs started to decompose at a gamma dose of 1 MGy, exhibiting a much lower tolerance to γradiation. At this radiation energy, the dominant interaction of the gamma-ray with MOFs is the Compton effect and the radiation stability of MOFs can be improved by prolific aromatic linkers, high linker connectivity, and good crystallinity. The results of this study indicate that MIL-100 and MIL-101 MOFs have a good potential to be employed in nuclear applications, where relatively high radiation doses play a role, for example, nuclear waste treatment and radionuclides production.

@en

The cerium-based metal–organic framework UiO-66 (Ce) was examined as a potential adsorbent for the ⁹⁹Mo/^99mTc generator. The results showed that the adsorbent had an outstanding adsorption performance, reaching up to 475 mg/g adsorption capacity at pH 3. An adsorption mechanism was proposed, where the adsorption was governed by hydrogen bonds, Ce-O-Mo coordination, π-anions and electrostatic interaction. Additionally, the adsorbent exhibited excellent radiation stability and good adsorption performance when radioactive ⁹⁹Mo was applied. A ⁹⁹Mo/^99mTc generator was fabricated with UiO-66 (Ce) as adsorbent and its performance was evaluated over two weeks. The elution results showed that 92 ± 3% of ^99mTc elution efficiency could be obtained with negligible cerium breakthrough, showing the great potential of UiO-66 (Ce) as adsorbent for ⁹⁹Mo/^99mTc generators.

@en

Background: Radionuclide therapy (RNT) has become a very important treatment modality for cancer nowadays. Comparing with other cancer treatment options, sufficient efficacy could be achieved in RNT with lower toxicity. β⁻ emitters are frequently used in RNT due to the long tissue penetration depth of the β⁻ particles. The dysprosium-166/holmium-166 (¹⁶⁶Dy/¹⁶⁶Ho) in vivo generator shows great potential for treating large malignancies due to the long half-life time of the mother nuclide ¹⁶⁶Dy and the emission of high energy β⁻ from the daughter nuclide ¹⁶⁶Ho. However, the internal conversion occurring after β⁻ decay from ¹⁶⁶Dy to ¹⁶⁶Ho could cause the release of about 72% of ¹⁶⁶Ho when ¹⁶⁶Dy is bound to conventional chelators. The aim of this study is to develop a nanoparticle based carrier for ¹⁶⁶Dy/¹⁶⁶Ho in vivo generator such that the loss of the daughter nuclide ¹⁶⁶Ho induced by internal conversion is prevented. To achieve this goal, we radiolabelled platinum-gold bimetallic nanoparticles (PtAuNPs) and core–shell structured gold nanoparticles (AuNPs) with ¹⁶⁶Dy and studied the retention of both ¹⁶⁶Dy and ¹⁶⁶Ho under various conditions. Results: The ¹⁶⁶Dy was co-reduced with gold and platinum precursor to form the ¹⁶⁶DyAu@AuNPs and ¹⁶⁶DyPtAuNPs. The ¹⁶⁶Dy radiolabelling efficiency was determined to be 60% and 70% for the two types of nanoparticles respectively. The retention of ¹⁶⁶Dy and ¹⁶⁶Ho were tested in MiliQ water or 2.5 mM DTPA for a period of 72 h. In both cases, more than 90% of both ¹⁶⁶Dy and ¹⁶⁶Ho was retained. The results show that the incorporation of ¹⁶⁶Dy in AuNPs can prevent the escape of ¹⁶⁶Ho released due to internal conversion. Conclusion: We developed a chelator-free radiolabelling method for ¹⁶⁶Dy with good radiolabelling efficiency and very high stability and retention of the daughter nuclide ¹⁶⁶Ho. The results from this study indicate that to avoid the loss of the daughter radionuclides by internal conversion, carriers composed of electron-rich materials should be used.

@en

The potential of the metal–organic framework UiO-66 and its functionalized derivatives for their utilization in the ⁹⁹Mo/^99mTc generator was assessed. Molybdenum adsorption experiments, structure characterization, molecular simulations and column experiments with molybdenum-99 were carried out. The results showed that the maximum molybdenum adsorption capacity achieved for UiO-66 was 335 mg g⁻¹. Adsorption on the surface of the UiO-66 occurs via electrostatic interaction and DFT calculations verified the enhanced affinity between the adsorbents and the molybdenum ions by Zr-O-Mo coordination, anion-π as well as hydrogen bonds. In addition, the performance of a ⁹⁹Mo/^99mTc generator fabricated with Form-UiO-66 was evaluated. The results showed that adsorption was comparable with the experiments using non-active molybdenum and that the ^99mTc elution efficiency of around 70% could be achieved without zirconium breakthrough.

@en

The Martian surface is constantly exposed to a high dose of cosmic radiation consisting of highly energetic particles and multiple types of ionizing radiation. The dose can increase temporarily by a factor of 50 through the occurrence of highly energetic solar flares. This may affect crop growth in greenhouses on the Martian surface possibly making settlement of humans more complicated. Shielding crops from radiation might be done at the expense of lighting efficiency. However, the most energy-efficient cultivation may be achieved through the use of natural daylight with the addition of LED lights. The goal of our research was to investigate whether Martian radiation, both the constant and the solar flares events, affects plant growth of two crop species, rye and garden cress. The levels of radiation received on the surface of Mars, simulated with an equivalent dose of ⁶⁰Co γ-photons, had a significant negative effect on the growth of the two crop species. Although germination percentages were not affected by radiation, biomass growth was significantly decreased by 32% for cress and 48% for rye during the first 4 weeks after germination. Part of the biomass differences may be due to differences in temperature between radiation and control treatment, however it cannot explain the whole difference between the treatment and control. Coloring of leaves, necrosis and brown parts, was observed as well. Temporary increases in ionizing radiation dose at different development stages of the plants did not significantly influence the final dry weight of the crops.

@en

Atomic layer deposition (ALD) is a versatile gas phase coating technique that allows coating of complex structured materials, as well as high-surface area materials such as nanoparticles. In this work, ALD is used to deposit a lutetium oxide layer on TiO₂ nanoparticles (P25) in a fluidized bed reactor to produce particles for nuclear medical applications. Two precursors were tested: the commercially available Lu(TMHD)₃ and the custom-made Lu(HMDS)₃. Using Lu(TMHD)₃, a lutetium loading up to 15 wt. % could be obtained, while using Lu(HMDS)₃, only 0.16 wt. % Lu could be deposited due to decomposition of the precursor. Furthermore, it was observed that vibration-assisted fluidization allows for better fluidization of the nanoparticles and hence a higher degree of coating.

@en

In this work, ^177mLu has been produced by irradiation of natural Lu₂O₃ targets at the BR2 reactor (Mol, Belgium) and the obtained data together with literature values have been used to theoretically investigate the production of ^177mLu at different neutron fluxes, irradiation times and enrichment of ¹⁷⁶Lu. The irradiation time (t_max) needed to reach the maximum ^177mLu production has been found to change from 42, 12, 4 days with the increase in the thermal neutron flux from 2*10¹⁴, 8*10¹⁴, 2.5*10¹⁵ n cm⁻² s⁻¹, respectively while keeping the maximum ^177mLu activity unaffected. The results of our calculations suggest that 0.11 TBq ^177mLu with a specific activity of 0.3 TBq g⁻¹ Lu can be produced in a short irradiation time of 4 days using 1g of 84.44% ¹⁷⁶Lu enriched Lu₂O₃ and a thermal neutron flux of 2.5*10¹⁵ n cm⁻² s⁻¹.

@en

New production routes for ⁹⁹Mo are steadily gaining importance. However, the obtained specific activity is much lower than currently produced by the fission of U-235. To be able to supply hospitals with ⁹⁹Mo/^99mTc generators with the desired activity, the adsorption capacity of the column material should be increased. In this paper we have investigated whether the gas phase coating technique Atomic Layer Deposition (ALD), which can deposit ultra-thin layers on high surface area materials, can be used to attain materials with high adsorption capacity for ⁹⁹Mo. For this purpose, ALD was applied on a silica-core sorbent material to coat it with a thin layer of alumina. This sorbent material shows to have a maximum adsorption capacity of 120 mg/g and has a^99mTc elution efficiency of 55 ± 2% based on 3 executive elutions.

@en

Different definitions for the concepts of information, information transfer, i.e. communication and its effect and efficiency of false, but also correct information, especially from the environmental sector, are given. "THE TEN ECOLOGICAL COMMANDMENTS"developed by Menke-Glückert at the end of the 1960s, the 9th commandment "Do not pollute information", in particular, is examined in more detail and understood practically as a currently unchanging law in our existing world societies. The "Ethics Consensus", derived from "THE TEN ECOLOGICAL COMMANDMENTS"and developed by Markert at the end of the 1990s, reflects both theoretical and practical levels of action that many people in our highly diverse world societies can support. From a scientific point of view, this article deals with the so-called B & B technologies, i.e. bioindication and biomonitoring of chemical elements, their chemical speciation as well as organic substances. B & B technologies, which deals with the biological detection of atmospheric deposition of chemical substances on a regional, national, and international level, are taken into account. From both an academic and a practical point of view, mosses have prevailed here in the last decades in addition to lichens. The use of mosses is a major focus of international air monitoring, especially in Europe. Furthermore, the phytoremediation of chemical substances in water, soil and air is described as a biological and sustainable biological process, which does not yet have the full scope as it is used in bioindication and biomonitoring, as shown in the example of mosses. However, the phytoremediation is considered to be an excellent tool to have the leading role in the sustainable pollutant "fight". In the future qualitative and quantitative approaches have been further developed to fit scientifically and practically B&B Technologies as well the different forms of phytotechnological approaches. Finally, the example of lithium, which is optionally derived from the Biological System of Chemical Elements (BSCE), becomes a chemical example that the administration of lithium to ALL mentally conditioned diseases such as manic depression to smoking cigarettes becomes one of the most valuable services for the recovery of human society on a global level. As a conclusion of these tremendous effects of lithium can be considered: Pulled out, to make clear that only this chemical element beside a psychiatric care and the involvement of family members, friends, physicians, psychologists and psychiatrists. In addition, it is a must that there is a strong relationship between patient, psychiatrist(s) and strongly related persons to the patient. First an intensive information transfer via communication must be guaranteed. After it, psychological support by doctors and, only if it seems necessary Lithium is to be given in a patient specific dose.

@en

A solid phase extraction based ^177mLu-¹⁷⁷Lu separation method has been investigated for its feasibility to be used in the radionuclide generator. The use of 2,2′,2”-(10-(2,6-dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid, (DOTAGA-anhydride) allowed grafting of DOTA (1,4,7,10-tetraazacyclododecane N,N′,N″,N‴-tetraacetic acid) complex on the surface of commercially available amino propyl silica. The grafting of DOTA has been confirmed by several characterization techniques. The thermogravimetric analysis reveals that the 0.33 mmol DOTA groups have been grafted per gram of silica. However, during the Lu ion complexation, a 10 times lower Lu adsorption capacity of 0.03 mmol g⁻¹ could be achieved under the studied reaction conditions. The results indicate that the grafting of DOTA on solid affects the Lu coordination and also influences the kinetics of Lu-DOTA complexation. The weak coordination resulted in high ^177mLu leakage, while the unreacted DOTA groups interfer with the ¹⁷⁷Lu release. This is evident from the 0.3% ^177mLu leakage combined with a¹⁷⁷Lu extraction efficiency of 25%. Overall, the results show a^177mLu-¹⁷⁷Lu separation with a maximum ¹⁷⁷Lu/^177mLu activity ratio of 25. But this is still far away from clinically acceptable activity ratio of 10,000 for which future work is recommended.

@en

In order to determine the potential of ^177mLu/¹⁷⁷Lu radionuclide generator in ¹⁷⁷Lu production it is important to establish the technical needs that can lead to a clinically acceptable ¹⁷⁷Lu product quality. In this work, a model that includes all the processes and the parameters affecting the performance of the ^177mLu/¹⁷⁷Lu radionuclide generator has been developed. The model has been based on the use of a ligand to complex ^177mLu ions, followed by the separation of the freed ¹⁷⁷Lu ions. The dissociation kinetics of the Lu-ligand complex has been found to be the most crucial aspect governing the specific activity and ^177mLu content of the produced ¹⁷⁷Lu. The dissociation rate constants lower than 1*10^-11 s^-1 would be required to lead to onsite ¹⁷⁷Lu production with specific activity close to theoretical maximum of 4.1 TBq ¹⁷⁷Lu/mg Lu and with ^177mLu content of less than 0.01%. Lastly, the calculations suggest that more than one patient dose per week can be supplied for a period of up to 7 months on starting with the ^177mLu produced using 3 g Lu₂O₃ target with 60% ¹⁷⁶Lu enrichment. The requirements of the starting ^177mLu activity production needs to be adapted depending on the required patient doses, and the technical specifications of the involved ^177mLu-¹⁷⁷Lu separation process.

@en

Cu is an important trace metal which plays a role in many biological processes. The radioisotope ⁶⁴Cu is often used to study such processes. Furthermore, ⁶⁴Cu finds applications in cancer diagnostics as well as therapy. For all of these applications ⁶⁴Cu having high specific activity is needed. ⁶⁴Cu can be produced in cyclotrons or in nuclear reactors. In this paper we study the effect of gamma dose on the production of ⁶⁴Cu according to the Szilard-Chalmers reaction using Cu(II)-phthalocyanine as a target. For this purpose, irradiations were performed in the nuclear reactor of the Delft University of Technology using a novel irradiation facility helping to limit the dose produced by gammas present in the reactor pool. The obtained ⁶⁴Cu activity yield was in general above 60% in accordance to the theoretical expected value. An increase in gamma dose has no significant influence on the obtained activity yield but increases the loss of Cu from Cu(II)-phthalocyanine up to 0.9% and hence decreases the specific activity that can be obtained. However, without optimisation, when reducing the gamma dose specific activities in the order of 30 TBq/g can be achieved.

@en

As a safer alternative for the use of radioactive tracers, the enriched stable 58Fe isotope has been introduced in studies of iron metabolism. In this study this isotope is measured with instrumental neutron activation analysis (INAA) in blood samples of patients with iron related disorders and controls after oral ingestion of a 58Fe containing pharmaceutical. Results were compared with those derived from MC-ICP-MS, applied on the same samples, and analytical and practical aspects of the two techniques were compared. Both techniques showed an increased absorption and incorporation in red blood cells of the 58Fe isotope in iron deficient patients in contrast to the controls. In all individuals results of INAA measurements were in good agreement with those of MC-ICP-MS ( |zeta| < 2 ). Uncertainties in INAA are substantially higher than those achievable by MC-ICP-MS but the INAA technique offers a high specificity and selectivity for iron close to 100%. In contrast to INAA, sample preparation before measurement is very critical in MC-ICP-MS and interferences with 58Ni and 54Cr may hamper the measurement of 58Fe and 54Fe respectively. Since it takes at least five days after irradiation to reduce the activity of interfering radionuclides (mainly 24Na), INAA is a more time consuming procedure; the need of a nuclear reactor facility makes it also less accessible than MC-ICP-MS. Costs are comparable. Both INAA and MC-ICP-MS are able to adequately measure changes in iron isotope composition in blood when an enriched stable iron isotope is applied in clinical research. Although MC-ICP-MS is more sensitive, is faster and has easier access, in INAA preparative steps before measurement are simpler and there are hardly demands on the kind and size of the samples. This may be relevant working with biomaterials in a clinical setting. @en

Background In this work, a lutetium-177 (177Lu) production method based on the separation of nuclear isomers, 177mLu & 177Lu, is reported. The 177mLu-177Lu separation is performed by combining the use of DOTA & DOTA-labelled peptide (DOTATATE) and liquid-liquid extraction. Methods The 177mLu cations were complexed with DOTA & DOTATATE and kept at 77 K for periods of time to allow 177Lu production. The freed 177Lu ions produced via internal conversion of 177mLu were then extracted in dihexyl ether using 0.01 M di-(2-ethylhexyl) phosphoric acid (DEHPA) at room temperature. The liquid-liquid extractions were performed periodically for a period up to 35 days. Results A maximum 177Lu/177mLu activity ratio of 3500 ± 500 was achieved with [177mLu]Lu-DOTA complex, in comparison to 177Lu/177mLu activity ratios of 1086 ± 40 realized using [177mLu]Lu-DOTATATE complex. The 177Lu-177mLu separation was found to be affected by the molar ratio of lutetium and DOTA. A 177Lu/177mLu activity ratio up to 3500 ± 500 was achieved with excess DOTA in comparison to 177Lu/177mLu activity ratio 1500 ± 600 obtained when lutetium and DOTA were present in molar ratio of 1:1. Further, the 177Lu ion extraction efficiency, decreases from 95 ± 4% to 58 ± 2% in the presence of excess DOTA. Conclusion The reported method resulted in a 177Lu/ 177mLu activity ratio up to 3500 after the separation. This ratio is close to the lower end of 177Lu/177mLu activity ratios, attained currently during the direct route 177Lu production for clinical applications (i.e. 4000–10,000). This study forms the basis for further extending the liquid-liquid extraction based 177mLu-177Lu separation in order to lead to a commercial 177mLu/177Lu radionuclide generator.@en

Background: While alpha microdosimetry dates back a couple of decades, the effects of localized energy deposition of alpha particles are often still unclear since few comparative studies have been performed. Most modern alpha microdosimetry studies rely for large parts on simulations, which negatively impacts both the simplicity of the calculations and the reliability of the results. A novel microdosimetry method based on the Fluorescent Nuclear Track Detector, a versatile tool that can measure individual alpha particles at sub-micron resolution, yielding accurate energy, fluence and dose rate measurements, was introduced to address these issues. Methods: Both the detectors and U87 glioblastoma cell cultures were irradiated using an external Am241 alpha source. The alpha particle tracks measured with a Fluorescent Nuclear Track Detector were used together with high resolution 3D cell geometries images to calculate the nucleus dose distribution in the U87 glioblastoma cells. The experimentally obtained microdosimetry parameters were thereafter applied to simulations of 3D U87 cells cultures (spheroids) with various spatial distributions of isotopes to evaluate the effect of the nucleus dose distribution on the expected cell survival. Results: The new experimental method showed good agreement with the analytically derived nucleus dose distributions. Small differences (<5%) in the relative effectiveness were found for isotopes in the cytoplasm and on the cell membrane versus external irradiation, while isotopes located in the nucleus or on the nuclear membrane showed a substantial increase in relative effectiveness (33 - 51%). Conclusions: The ease-of-use, good accuracy and use of experimentally derived characteristics of the radiation field make this method superior to conventional simulation-based microdosimetry studies. Considering the uncertainties found in alpha radionuclide carriers in-vivo and in-vitro, together with the large contributions from the relative biological effectiveness and the oxygen enhancement ratio, it is expected that only carriers penetrating or surrounding the cell nucleus will substantially benefit from microdosimetry.@en

Introduction: The use of 225Ac for alpha radionuclide therapy is a relatively novel approach, where the dense energy deposition of alpha radiation is used to treat cancer more effectively. 225Ac has, compared to conventional radionuclides, a long half-life of 10 days and a long decay chain, yielding 4 alpha particles, 2 beta particles and several gamma rays. This long decay chain presents new challenges. Daughter radionuclides that separate from the radionuclide carrier during radioactive decay can end up freely circulating …@en

Structured illumination microscopy (SIM) for the imaging of alpha particle tracks in fluorescent nuclear track detectors (FNTD) was evaluated and compared to confocal laser scanning microscopy (CLSM). FNTDs were irradiated with an external alpha source and imaged using both methodologies. SIM imaging resulted in improved resolution, without increase in scan time. Alpha particle energy estimation based on the track length, direction and intensity produced results in good agreement with the expected alpha particle energy distribution. A pronounced difference was seen in the spatial scattering of alpha particles in the detectors, where SIM showed an almost 50% reduction compared to CLSM. The improved resolution of SIM allows for more detailed studies of the tracks induced by ionising particles. The combination of SIM and FNTDs for alpha radiation paves the way for affordable and fast alpha spectroscopy and dosimetry. Journal compilation

@en