Effects of High Gamma Doses on the Structural Stability of Metal-Organic Frameworks.

Four different MOFs were exposed to γ rays 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 γ radiation. 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.

Characterization of selenium-enriched wheat by agronomic biofortification.

Agronomic biofortification of staple crops is an effective way to enhance their contents in essential nutrients up the food chain, with a view to correcting for their deficiencies in animal or human status. Selenium (Se) is one such case, for its uneven distribution in the continental crust and, therefore, in agricultural lands easily translates into substantial variation in nutritional intakes. Cereals are far from being the main sources of Se on a content basis, but they are likely the major contributors to intake on a dietary basis. To assess their potential to assimilate and biotransform Se, bread and durum wheat were enriched with Se through foliar and soil addition at an equivalent field rate of 100 g of Se per hectare (ha), using sodium selenate and sodium selenite as Se-supplementation matrices, in actual field conditions throughout. Biotransformation of inorganic Se was evaluated by using HPLC-ICP-MS after enzymatic hydrolysis for Se-species extraction in the resulting mature wheat grains. Selenomethionine and Se(VI) were identified and quantified: the former was the predominant species, representing 70-100 % of the total Se in samples; the maximum amount of inorganic Se was below 5 %. These results were similar for both supplementation methods and for both wheat varieties. Judging from the present results, one can conclude that agronomic biofortification of wheat may improve the nutritional quality of wheat grains with significant amounts of selenomethionine, which is an attractive option for increasing the Se status in human diets through Se-enriched, wheat-based foodstuff.

(89)Zr-labeled paramagnetic octreotide-liposomes for PET-MR imaging of cancer.

PURPOSE: Dual-modality PET/MR platforms add a new dimension to patient diagnosis with high resolution, functional, and anatomical imaging. The full potential of this emerging hybrid modality could be realized by using a corresponding dual-modality probe. Here, we report pegylated liposome (LP) formulations, housing a MR T(1) contrast agent (Gd) and the positron-emitting (89)Zr (half-life: 3.27 days), for simultaneous PET and MR tumor imaging capabilities. METHODS: (89)Zr oxophilicity was unexpectedly found advantageous for direct radiolabeling of preformed paramagnetic LPs. LPs were conjugated with octreotide to selectively target neuroendocrine tumors via human somatostatin receptor subtype 2 (SSTr2). (89)Zr-Gd-LPs and octreotide-conjugated homolog were physically, chemically and biologically characterized. RESULTS: (89)Zr-LPs showed reasonable stability over serum proteins and chelator challenges for proof-of-concept in vitro and in vivo investigations. Nuclear and paramagnetic tracking quantified superior SSTr2-recognition of octreotide-LP compared to controls. CONCLUSIONS: This study demonstrated SSTr2-targeting specificity along with direct chelator-free (89)Zr-labeling of LPs and dual PET/MR imaging properties.

Integration of biomonitoring and instrumental techniques to assess the air quality in an industrial area located in the coastal of central Asturias, Spain.

Throughout the world, epidemiological studies were established to examine the relationship between air pollution and mortality rates and adverse respiratory health effects. However, despite the years of discussion the correlation between adverse health effects and atmospheric pollution remains controversial, partly because these studies are frequently restricted to small and well-monitored areas. Monitoring air pollution is complex due to the large spatial and temporal variations of pollution phenomena, the high costs of recording instruments, and the low sampling density of a purely instrumental approach. Therefore, together with the traditional instrumental monitoring, bioindication techniques allow for the mapping of pollution effects over wide areas with a high sampling density. In this study, instrumental and biomonitoring techniques were integrated to support an epidemiological study that will be developed in an industrial area located in Gijon in the coastal of central Asturias, Spain. Three main objectives were proposed to (i) analyze temporal patterns of PM10 concentrations in order to apportion emissions sources, (ii) investigate spatial patterns of lichen conductivity to identify the impact of the studied industrial area in air quality, and (iii) establish relationships amongst lichen conductivity with some site-specific characteristics. Samples of the epiphytic lichen Parmelia sulcata were transplanted in a grid of 18 by 20 km with an industrial area in the center. Lichens were exposed for a 5-mo period starting in April 2010. After exposure, lichen samples were soaked in 18-MΩ water aimed at determination of water electrical conductivity and, consequently, lichen vitality and cell damage. A marked decreasing gradient of lichens conductivity relative to distance from the emitting sources was observed. Transplants from a sampling site proximal to the industrial area reached values 10-fold higher than levels far from it. This finding showed that lichens reacted physiologically in the polluted industrial area as evidenced by increased conductivity correlated to contamination level. The integration of temporal PM10 measurements and analysis of wind direction corroborated the importance of this industrialized region for air quality measurements and identified the relevance of traffic for the urban area.

Molybdenum incorporation in tungsten aldehyde oxidoreductase enzymes from Pyrococcus furiosus.

The hyperthermophilic archaeon Pyrococcus furiosus expresses five aldehyde oxidoreductase (AOR) enzymes, all containing a tungsto-bispterin cofactor. The growth of this organism is fully dependent on the presence of tungsten in the growth medium. Previous studies have suggested that molybdenum is not incorporated in the active site of these enzymes. Application of the radioisotope (99)Mo in metal isotope native radioautography in gel electrophoresis (MIRAGE) technology to P. furiosus shows that molybdenum can in fact be incorporated in all five AOR enzymes. Mo(V) signals characteristic for molybdopterin were observed in formaldehyde oxidoreductase (FOR) in electron paramagnetic resonance (EPR)-monitored redox titrations. Our finding that the aldehyde oxidation activity of FOR and WOR5 (W-containing oxidoreductase 5) correlates only with the residual tungsten content suggests that the Mo-containing AORs are most likely inactive. An observed W/Mo antagonism is indicative of tungstate-dependent negative feedback of the expression of the tungstate/molybdate ABC transporter. An intracellular selection mechanism for tungstate and molybdate processing has to be present, since tungsten was found to be preferentially incorporated into the AORs even under conditions with comparable intracellular concentrations of tungstate and molybdate. Under the employed growth conditions of starch as the main carbon source in a rich medium, no tungsten- and/or molybdenum-associated proteins are detected in P. furiosus other than the high-affinity transporter, the proteins of the metallopterin insertion machinery, and the five W-AORs.

Solid phase extraction-based separation of the nuclear isomers 177mLu and 177Lu.

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 a177mLu-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.

Modelling of the 177mLu/177Lu radionuclide generator.

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.

Lanthanide(III) complexes of bis(phosphonate) monoamide analogues of DOTA: bone-seeking agents for imaging and therapy.

Lanthanide complexes of DOTA derivatives 2a (BPAMD) and 2b (BPAPD), having a monoamide pendant arm with a bis(phosphonate) moiety, were comparatively tested for application in MRI, radiotherapy, and bone pain palliation. (1)H, (31)P, and (17)O NMR spectroscopy show that they are nine-coordinated, with one water molecule in the first coordination sphere of the Ln(III) ion. The bis(phosphonate) moieties are not coordinated to the lanthanide and predominantly mono- and diprotonated at physiological pH. The parameters governing the longitudinal relaxivities of the Gd complexes are similar to those of other monoamides of DOTA reported in the literature. Upon adsorption on hydroxyapatite, the relaxivities at 20 MHz and 25 degrees C of Gd-2a and Gd-2b were 22.1 and 11 s(-1) mM(-1), respectively. An in vivo gamma-ray imaging study showed that the (177)Lu complexes of 2a and 2b have a high affinity for bones, particularly for growth plates and teeth with a prolonged retention.

Towards the production of carrier-free 99Mo by neutron activation of 98Mo in molybdenum hexacarbonyl -Szilard-Chalmers enrichment.

The neutron irradiation of molybdenum hexacarbonyl has been systematically studied to identify possible improvements for the production of molybdenum-99. After irradiation, the targets were dissolved in dichloromethane, and Szilard-Chalmers liquid-liquid extraction was carried out with aqueous extractants. The effects of the irradiation time, the aqueous phase composition and the irradiated mass were studied with a focus on the chemistry involved. Stable extraction yields of 20% were obtained with enrichment decreasing with target decomposition. Improved enrichment requires decreased decomposition.

A Critical Review of Alpha Radionuclide Therapy-How to Deal with Recoiling Daughters?

This review presents an overview of the successes and challenges currently faced in alpha radionuclide therapy. Alpha particles have an advantage in killing tumour cells as compared to beta or gamma radiation due to their short penetration depth and high linear energy transfer (LET). Touching briefly on the clinical successes of radionuclides emitting only one alpha particle, the main focus of this article lies on those alpha-emitting radionuclides with multiple alpha-emitting daughters in their decay chain. While having the advantage of longer half-lives, the recoiled daughters of radionuclides like 224Ra (radium), 223Ra, and 225Ac (actinium) can do significant damage to healthy tissue when not retained at the tumour site. Three different approaches to deal with this problem are discussed: encapsulation in a nano-carrier, fast uptake of the alpha emitting radionuclides in tumour cells, and local administration. Each approach has been shown to have its advantages and disadvantages, but when larger activities need to be used clinically, nano-carriers appear to be the most promising solution for reducing toxic effects, provided there is no accumulation in healthy tissue.

Enhanced retention of encapsulated ions in cross-linked polymersomes.

Polymer vesicles (polymersomes) composed of poly(butadiene-b-poly(ethylene oxide)) (PB-b-PEO) are known for their stability and limited permeability. However, when these vesicles are diluted, substances, such as ions, encapsulated in the aqueous cavity can be released due to vesicle disruption. In previous studies, we have shown that these vesicles can be loaded efficiently with sufficient quantities of radionuclides to allow application in radionuclide therapy and pharmacokinetics evaluation, provided that there is no loss of the encapsulated radionuclides when diluted in the bloodstream. In this paper, in order to stabilize the carriers, we propose to cross-link the hydrophobic part of the polymersome membrane and to investigate whether such cross-linking induced by γ radiation can enhance the retention of ions (radionuclides). Retention of ions encapsulated in the lumen in such cross-linked carriers has not been previously quantitatively evaluated, although it is of ultimate importance in any medical application. Here, we also investigate how cross-linking affects the transport of radionuclides (loading) through the membrane of the vesicles. The integrity of the vesicles as a function of the radiation dose is also investigated, including morphological changes. The results show that cross-linking hinders the transport of ions through the membrane, which also leads to higher retention of ions encapsulated prior to cross-linking in the vesicles. Electron micrographs show that the shape of the polymersomes is not greatly affected by γ radiation when left in the original solvent (phosphate buffered saline (PBS) or Milli-Q water), but when diluted in a good solvent for both blocks, i.e., tetrahydrofuran (THF), disintegration of the vesicles and the appearance of droplet-like structures is observed, which had not been reported previously. The results of the present study help to formulate polymersomes as carriers for radionuclide therapy, demonstrating a way to prevent in vivo release of radionuclides, caused by dilution-induced destabilization of the nanocarriers.

Accurate assessment of whole-body retention for PRRT with (177)Lu using paired measurements with external detectors.

The aim of this study was to assess the accuracy of the results of whole-body measurements by comparison with the urine collection method in the PRRT with (177)Lu and furthermore to develop a more accurate method of paired measurements. Excreted samples were collected at given intervals and activities were measured by a dose calibrator. Traditionally, whole-body activities during subsequent measurements are normalized individually to the administered activity. In order to correct for the effects of the activity in the bladder during the baseline measurement before the first voiding and activity redistributions in the patient body during subsequent measurements, a series of paired measurements before and after each voiding were carried out. Time-dependent detector responses at given times were derived and time-activity retentions were then determined. Compared to the results of the urine collection, whole-body activities by traditional whole-body measurements were overestimated by ca. 14% at 1 h after administration and randomly varied from -29% to 49% at 24 h. Measurement uncertainties of whole-body activities were from ± 4% (the coverage factor k=2) at 1 h to >± 20% at 24 h by the urine collection and ± 7% by paired measurements, respectively. Whole-body activities at 1 h by paired measurements were validated using the results by measurements of the collected first urine. The new method of paired measurements has an equivalent measurement accuracy and even better during the later measurements with respect to the urine collection method and therefore can replace urine approach for assessing the time-activity remaining in the patient body.

The necessity of nuclear reactors for targeted radionuclide therapies.

Nuclear medicine has been contributing towards personalized therapies. Nuclear reactors are required for the working horses of both diagnosis and treatment, i.e., Tc-99m and I-131. In fact, reactors will remain necessary to fulfill the demand for a variety of radionuclides and are essential in the expanding field of targeted radionuclide therapies for cancer. However, the main reactors involved in the global supply are ageing and expected to shut down before 2025. Therefore, the fields of (nuclear) medicine, nuclear industry and politics share a global responsibility, faced with the task to secure future access to suitable nuclear reactors. At the same time, alternative production routes should be industrialized. For this, a coordinating entity should be put into place.

Cell-membrane damage and element leaching in transplanted Parmelia sulcata lichen related to ambient SO2, temperature, and precipitation.

Measurements were performed in lichen (Parmelia sulcata) transplants, to gain insight into the lichen vitality as possibly affected by both element deposition or lichen element content and further ambient atmospheric conditions (temperature, precipitation, SO2 levels). The electrical conductivity of rinsing solutions was used to assess cell-membrane damage in Parmelia sulcata in an experiment, which ran from August 2001 until August 2002. Element contents of the solutions and lichens were determined by inductively coupled plasma-optical emission spectrometry and by k0-instrumental neutron activation analysis, respectively. Factor analysis (MCATTFA) was used to determine grouping of elements of similar origin and/ or behavior. All in all, the data indicate that, apartfrom lichen Na and Cl levels, and for temperature and precipitation, no clear relationships with conductivity could be observed. Conductivity was mostly related to released Na, Cl, K, Mg, and Cs. On the basis of concentrations, Na, Cl, and K could be considered as largely determining the conductivity. The data suggest a different origin for K than that for Na and Cl: the latter two are most probably due to effects from sea salt sprays. Parmelia sulcata was sensitive enough to reflect appreciable ambient rises in air SO2 and resistant enough to recover afterward. MCATTFA on selected elements (K, Sc, Cu, V, As, and Sb) indicated the absence of any comparability between K and V, As and Sb, suggesting differences in origin and/or chemico-physical occurrence. Generally speaking, the present data suggest that the comparability of lichen vitality in large geographical areas may be limited and governed by the area's variability in temperature and precipitation rather than by variability in metal deposition rates. The leaching data on all elements and element groups, however, strongly suggest that wet deposition may also severely affect lichen elemental levels. This latter observation means that comparing outcomes for time or spatial series of lichen samples should be accompanied by a comparably careful monitoring of (preceding) ambient conditions.