Electromagnetic Fields Exposure Assessment in Europe Utilizing Publicly Available Data.

The ever-increasing use of wireless communication systems during the last few decades has raised concerns about the potential health effects of electromagnetic fields (EMFs) on humans. Safety limits and exposure assessment methods were developed and are regularly updated to mitigate health risks. Continuous radiofrequency EMF monitoring networks and in situ measurement campaigns provide useful information about environmental EMF levels and their variations over time and in different microenvironments. In this study, published data from the five largest monitoring networks and from two extensive in situ measurement campaigns in different European countries were gathered and processed. Median electric field values for monitoring networks across different countries lay in the interval of 0.67-1.51 V/m. The median electric field value across different microenvironments, as evaluated from in situ measurements, varied from 0.10 V/m to 1.42 V/m. The differences between networks were identified and mainly attributed to variations in population density. No significant trends in the temporal evolution of EMF levels were observed. The influences of parameters such as population density, type of microenvironment, and height of measurement on EMF levels were investigated.

Competing Metal-Ligand Interactions in Tris(cyclopentadienyl)-cyclohexylisonitrile Complexes of Trivalent Actinides and Lanthanides.

The structure and bonding properties of 16 complexes formed by trivalent f elements (M=U, Np, Pu and lanthanides except for Pm and Pr) with cyclopentadienyl (Cp) and cyclohexylisonitrile (C≡NCy) ligands, (Cp)3M(C≡NCy), were studied by a joint experimental (XRD, NMR) and theoretical (DFT) analysis. For the large La(III) ion, the bis-adduct (Cp)3La(C≡NCy)2 could also be synthesized and characterized. The metal-ligand interactions, focusing on the comparison of the actinides and lanthanides as well as on the competition of the two different ligands for M, were elucidated using the Quantum Theory of Atoms in Molecules (QTAIM) and Natural Bond Orbital (NBO) models. The results point to interactions of comparable strengths with the anionic Cp and neutral C≡NCy ligands in the complexes. The structural and bonding properties of the actinide complexes reflect small but characteristic differences with respect to the lanthanide analogues. They include larger ligand-to-metal charge transfers as well as metal-ligand electron-sharing interactions. The most significant experimental marker of these covalent interactions is the C≡N stretching frequency.

Dosing 225Ac-DOTATOC in patients with somatostatin-receptor-positive solid tumors: 5-year follow-up of hematological and renal toxicity.

PURPOSE: The aim of this retrospective analysis is to estimate the most appropriate single cycle and cumulative doses of 225Ac-DOTATOC in patients treated for somatostatin-receptor-expressing cancers. METHODS: 225Ac-DOTATOC was administered to thirty-nine patients with various somatostatin-receptor-positive tumors. Baseline and follow-up 68Ga-DOTATOC PET/CT, lab tests, and renal scintigraphy were obtained. Patients received long-term follow-up either at the local cancer center or in close collaboration with external oncologists. Acute and chronic hematological toxicity was evaluated quantitatively over time. Long-term follow-up of creatinine was used to approximate the annual loss of estimated GFR (eGFR). RESULTS: Dose-dependent acute hematological toxicity was seen at single doses above 40 MBq or repeated doses greater than approximately 20 MBq 225Ac-DOTATOC at 4 month intervals. Treatment-related kidney failure occurred in 2 patients after a delay of >4 years but was independent of administered radioactivity, and other clinical risk factors were important contributors to renal decline. In general, the annual decline of eGFR among patients did not follow a clear dose-effect relationship even in patients with previous ß-therapy. An average eGFR-loss of 8.4ml/min (9.9%) per year was observed which is similar to the experience with ß-therapy studies. CONCLUSION: Treatment activities of approx. 20 MBq per cycle (4 monthly repetition) and cumulative doses up to 60-80 MBq generally avoided both acute and chronic grade 3/4 hematotoxicity in patients with advanced stage malignancies. Chronic renal toxicity was observed at these doses, but pre-existing renal risk factors were important co-factors. These data represent a starting point for additional research to more precisely define safety thresholds of 225Ac-DOTATOC.

Tris-{hydridotris(1-pyrazolyl)borato}actinide Complexes: Synthesis, Spectroscopy, Crystal Structure, Bonding Properties and Magnetic Behaviour.

The isostructural compounds of the trivalent actinides uranium, neptunium, plutonium, americium, and curium with the hydridotris(1-pyrazolyl)borato (Tp) ligand An[η3 -HB(N2 C3 H3 )3 ]3 (AnTp3 ) have been obtained through several synthetic routes. Structural, spectroscopic (absorption, infrared, laser fluorescence) and magnetic characterisation of the compounds were performed in combination with crystal field, density functional theory (DFT) and relativistic multiconfigurational calculations. The covalent bonding interactions were analysed in terms of the natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) models.

Safety and efficacy of targeted alpha therapy with 213Bi-DOTA-substance P in recurrent glioblastoma.

Treatment options for recurrent glioblastoma multiforme (GBM) are very limited. GBM cells express high levels of the GPCR neurokinin type 1 receptor (NK-1R), and a modified substance P can be used as its ligand for the tumor cell targeting. Targeted alpha therapy with DOTA-Substance P labeled with the short range alpha emitter 213Bi allows for selective irradiation and killing of tumor cells. MATERIAL AND METHODS: Twenty patients with recurrent GBM were included into the study following a standard therapy. 1-2 intracavitary or intratumoral port-a-cath systems were stereotactically inserted. Patients were treated with 1-7 doses of 213Bi-DOTA-Substance P (213Bi-DOTA-SP) in 2-month intervals. 68Ga-DOTA-Substance P (68Ga-DOTA-SP) was co-injected with 213Bi-DOTA-SP to assess the biodistribution using PET/CT. Therapeutic response was monitored with performance status and MRI imaging. RESULTS: Treatment with activity up to 11.2 GBq 213Bi-DOTA-SP was well tolerated with only mild and transient adverse reactions. The median progression free survival was 2.7 months. The median overall survival from the first diagnosis was 23.6 months and median survival after recurrence was 10.9 months. The median survival time from the start of 213Bi-DOTA-SP was 7.5 months. CONCLUSIONS: Treatment of recurrent GBM with 213Bi-DOTA-SP is safe and well tolerated. The median overall survival after recurrence of 10.9 months compares favorably to the available alternative treatment options. Once the supply of high activity 225Ac/213Bi radionuclide generators is secured, targeted alpha therapy with 213Bi-DOTA-SP may evolve as a promising novel option to treat recurrent GBM.

Prolonged survival in secondary glioblastoma following local injection of targeted alpha therapy with 213Bi-substance P analogue.

BACKGROUND: Glioblastoma multiforme (GBM), the most common malignant brain tumor, mainly manifests as a primary de novo and less frequently as a secondary glial neoplasm. GBM has been demonstrated to overexpress the NK-1 receptor and substance P can be used as a ligand for targeted therapy. Alpha emitters, e.g. 213Bi, that deposit their high energy within a short range allow the selective irradiation of tumor cells while sparing adjacent neuronal structures. MATERIAL AND METHODS: Among 50 glioma patients of different subtypes that have to date been treated with targeted alpha therapy at the Medical University Warsaw, we report here the data on nine patients with secondary GBM. Following surgery, chemo- and radiotherapy, recurrent GBM was treated by intracavitary injection of 1-6 doses of 0.9-2.3 GBq 213Bi- DOTA-[Thi8,Met(O2)11]-substance P (213Bi-DOTA-SP) in 2-month intervals. 68Ga-DOTA-[Thi8,Met(O2)11]-substance P (68Ga-DOTA-SP) was co-injected with the therapeutic doses to assess biodistribution using PET/CT. Therapeutic response was monitored with MRI. RESULTS: Treatment with activities ranging from 1.4 to 9.7 (median 5.8) GBq 213Bi- DOTA-SP was well tolerated with only mild transient adverse reactions, mainly headaches due to a transient perfocal edema reaction. The median progression free survival and overall survival time following the initiation of alpha therapy was 5.8 and 16.4 months, respectively. The median overall survival time from the first diagnosis was 52.3 months. Two out of nine patients are still alive 39 and 51 months, respectively, after the initiation of the therapy. CONCLUSIONS: Targeted alpha therapy of secondary GBM with 213Bi-DOTA-SP is safe and well tolerated and may evolve as a promising novel therapeutic option for secondary GBM.

Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter immunoconjugate targeting the epidermal growth factor receptor: a pilot study.

PURPOSE: Patients with carcinoma in situ (CIS) of the bladder refractory to bacillus Calmette-Guérin (BCG) treatment are usually treated with cystectomy. Therefore, new treatment options with preservation of the urinary bladder are needed. The objective of the study was to investigate the feasibility, safety and efficacy of a novel targeted alpha-emitter immunotherapy for CIS after BCG treatment failure. METHODS: A pilot study was conducted in 12 patients (age range 64-86 years, ten men, two women) with biopsy-proven CIS of the bladder refractory to BCG treatment. The patients were treated intravesically with a single instillation (one patient was treated twice) of the alpha-emitter 213Bi coupled to an anti-EGFR antibody (366-821 MBq). The primary aims of the study were to determine the feasibility of treatment with the 213Bi-immunoconjugate and evaluation of adverse effects. Therapeutic efficacy was monitored by histological mapping of the urinary bladder 8 weeks after treatment and at different time points thereafter. RESULTS: The study proved that intravesical instillation of the 213Bi-immunoconjugate targeting EGFR is feasible. No adverse effects were observed and all blood and urine parameters determined remained in their normal ranges. Therapeutic efficacy was considered satisfactory, in that three of the 12 patients showed no signs of CIS 44, 30 and 3 months after treatment. CONCLUSION: Intravesical instillation of 213Bi-anti-EGFR monoclonal antibody was well tolerated and showed therapeutic efficacy. Repeated instillation and/or instillation of higher activities of the 213Bi-immunoconjugate might lead to better therapeutic outcomes. A phase I clinical trial is planned.

Solid-State Structure of Tris-Cyclopentadienide Uranium(III) and Plutonium(III).

The organometallic tris-cyclopentadienide actinide(III) (AnCp3 ) complexes were first reported about 50 years ago. However, up until now, only the NpCp3 solid state structure has been studied. Here we report on the solid state structures of UCp3 and PuCp3 which are isostructural to the Np analogue. The structural models are supported by theoretical calculations and compared to their lanthanide analogues. The observed trends in changes of bond lengths might be indicator for an increased covalency in the bonding in the tris-cyclopentadienide actinide(III) complexes (AnCp3 ) compared to their lanthanide homologues.

A Structurally Characterized Organometallic Plutonium(IV) Complex.

The blood-red plutonocene complex Pu(1,3-COT'')(1,4-COT'') (4; COT''=η8 -bis(trimethylsilyl)cyclooctatetraenyl) has been synthesized by oxidation of the anionic sandwich complex Li[Pu(1,4-COT'')2 ] (3) with anhydrous cobalt(II) chloride. The first crystal structure determination of an organoplutonium(IV) complex revealed an asymmetric sandwich structure for 4 where one COT'' ring is 1,3-substituted while the other retains the original 1,4-substitution pattern. The electronic structure of 4 has been elucidated by a computational study, revealing a probable cause for the unexpected silyl group migration.

Subtle Interactions and Electron Transfer between U(III) , Np(III) , or Pu(III) and Uranyl Mediated by the Oxo Group.

A dramatic difference in the ability of the reducing An(III) center in AnCp3 (An=U, Np, Pu; Cp=C5 H5 ) to oxo-bind and reduce the uranyl(VI) dication in the complex [(UO2 )(THF)(H2 L)] (L="Pacman" Schiff-base polypyrrolic macrocycle), is found and explained. These are the first selective functionalizations of the uranyl oxo by another actinide cation. At-first contradictory electronic structural data are explained by combining theory and experiment. Complete one-electron transfer from Cp3 U forms the U(IV) -uranyl(V) compound that behaves as a U(V) -localized single molecule magnet below 4 K. The extent of reduction by the Cp3 Np group upon oxo-coordination is much less, with a Np(III) -uranyl(VI) dative bond assigned. Solution NMR and NIR spectroscopy suggest Np(IV) U(V) but single-crystal X-ray diffraction and SQUID magnetometry suggest a Np(III) -U(VI) assignment. DFT-calculated Hirshfeld charge and spin density analyses suggest half an electron has transferred, and these explain the strongly shifted NMR spectra by spin density contributions at the hydrogen nuclei. The Pu(III) -U(VI) interaction is too weak to be observed in THF solvent, in agreement with calculated predictions.

Branched amphiphilic peptide capsules: cellular uptake and retention of encapsulated solutes.

Branched amphiphilic peptide capsules (BAPCs) are peptide nano-spheres comprised of equimolar proportions of two branched peptide sequences bis(FLIVI)-K-KKKK and bis(FLIVIGSII)-K-KKKK that self-assemble to form bilayer delimited capsules. In two recent publications we described the lipid analogous characteristics of our BAPCs, examined their initial assembly, mode of fusion, solute encapsulation, and resizing and delineated their capability to be maintained at a specific size by storing them at 4°C. In this report we describe the stability, size limitations of encapsulation, cellular localization, retention and, bio-distribution of the BAPCs in vivo. The ability of our constructs to retain alpha particle emitting radionuclides without any apparent leakage and their persistence in the peri-nuclear region of the cell for extended periods of time, coupled with their ease of preparation and potential tune-ability, makes them attractive as biocompatible carriers for targeted cancer therapy using particle emitting radioisotopes. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.

Ultra-small plutonium oxide nanocrystals: an innovative material in plutonium science.

Apart from its technological importance, plutonium (Pu) is also one of the most intriguing elements because of its non-conventional physical properties and fascinating chemistry. Those fundamental aspects are particularly interesting when dealing with the challenging study of plutonium-based nanomaterials. Here we show that ultra-small (3.2±0.9 nm) and highly crystalline plutonium oxide (PuO2 ) nanocrystals (NCs) can be synthesized by the thermal decomposition of plutonyl nitrate ([PuO2 (NO3 )2 ]⋅3 H2 O) in a highly coordinating organic medium. This is the first example reporting on the preparation of significant quantities (several tens of milligrams) of PuO2 NCs, in a controllable and reproducible manner. The structure and magnetic properties of PuO2 NCs have been characterized by a wide variety of techniques (powder X-ray diffraction (PXRD), X-ray absorption fine structure (XAFS), X-ray absorption near edge structure (XANES), TEM, IR, Raman, UV/Vis spectroscopies, and superconducting quantum interference device (SQUID) magnetometry). The current PuO2 NCs constitute an innovative material for the study of challenging problems as diverse as the transport behavior of plutonium in the environment or size and shape effects on the physics of transuranium elements.

Controlled synthesis of thorium and uranium oxide nanocrystals.

Very little is known about the size and shape effects on the properties of actinide compounds. As a consequence, the controlled synthesis of well-defined actinide-based nanocrystals constitutes a fundamental step before studying their corresponding properties. In this paper, we report on the non-aqueous surfactant-assisted synthesis of thorium and uranium oxide nanocrystals. The final characteristics of thorium and uranium oxide nanocrystals can be easily tuned by controlling a few experimental parameters such as the nature of the actinide precursor and the composition of the organic system (e.g., the chemical nature of the surfactants and their relative concentrations). Additionally, the influence of these parameters on the outcome of the synthesis is highly dependent on the nature of the actinide element (thorium versus uranium). By using optimised experimental conditions, monodisperse isotropic uranium oxide nanocrystals with different sizes (4.5 and 10.7 nm) as well as branched nanocrystals (overall size ca. 5 nm), nanodots (ca. 4 nm) and nanorods (with ultra-small diameters of 1 nm) of thorium oxide were synthesised.

catena-Poly[[tris-(acetonitrile-κN)praseodymium(III)]tris-(µ-trifluoro-methane-sulfonato-κ(2) O:O')].

In the colourless title compound, [Pr(CF3O3S)3(CH3CN)3] n , the three trifluoro-methane-sulfonate anions form three bridges via O:O'-coordination between two Pr(III) atoms. The structure contains [Pr(NCMe)3-µ2(OTf)3-Pr(NCMe)3-µ2(OTf)3] n (NCMe is acetonitrile; OTf is trifluoromethanesulfonate) chains parallel to the a axis. The Pr(III) atom is nine-coordinate in a distorted tricapped trigonal-prismatic environment.

A study of the long term changes in the electromagnetic environment using data from continuous monitoring sensors in Greece.

Owing to the advancement of wireless technologies, there is a strong public perception of increasing exposure to Radiofrequency (RF) electromagnetic fields (EMF). The aim of this study is to determine the evolution of EMF in the environment, and consequently, human exposure to them, over a period of about two decades, spanning from the end of 2003 until February 2022. The study is based on data collected by two non-ionizing radiation monitoring networks in Greece. The networks consist of fixed EMF sensors that register the RMS electric field value every 6 min, on a 24 h basis. We used the Seasonal-Trend decomposition method using (LOESS), known as the STL method to decompose the time series into trend, seasonal, and noise components. Additionally, since the sensors include frequency filters for separating the cellular frequencies, the recorded data were used to identify the exposure contribution by cellular networks in comparison to other EMF sources. The study indicates that RF-EMF do not explicitly decrease or increase but rather fluctuate over time. Similarly, the contribution of mobile cellular networks to the total field change over time.

fac-Bromidotricarbonyl[2-(diisopropylphosphanyl)benzaldehyde-κ(2)O,P]rhenium(I).

The structure of the title complex, [ReBr(C(13)H(19)OP)(CO)(3)], displays a facial coordination of the three CO ligands and a κ(2)O,P coordination mode of the 2-diisopropyl-phosphino-benzaldehyde ligands. The Re-C bond distance for the CO ligand trans to the P atom is, due to its trans influence, elongated to 1.943 (3) Å, showing that this CO ligand is more weakly bound to the Re centre than the other two.

Differential gene expression triggered by highly cytotoxic alpha-emitter-immunoconjugates in gastric cancer cells.

Immunoconjugates composed of the alpha-emitter (213)Bi and the monoclonal antibody d9MAb specifically target HSC45-M2 gastric cancer cells expressing mutant d9-E-cadherin. These conjugates efficiently killed tumor cells in a nude mouse peritoneal carcinomatosis model. To elucidate the molecular responses of HSC45-M2 cells to alpha-emitter irradiation, whole genome gene expression profiling was performed. For that purpose HSC45-M2 cells were incubated with lethal doses of (213)Bi-d9MAb. RNA was isolated at 6, 24 and 48 h after irradiation, transcribed into cDNA and hybridized to whole genome microarrays. Results of microarray analysis were validated using RTQ-PCR showing correspondence of approximately 90%. Following incubation with (213)Bi-d9MAb, 682-1125 genes showed upregulation and 666-1278 genes showed downregulation at one time point, each. Eight genes appeared upregulated and 12 genes downregulated throughout. Molecular functions and biological processes of differentially expressed genes were categorized according to the PANTHER database. Following (213)Bi-d9MAb irradiation also a time-dependent shift in terms of overrepresentation of biological processes was observed. Among the genes showing continuous upregulation, COL4A2, NEDD9 and C3 have not been associated with the cellular response to high LET radiation so far. The same holds true for WWP2, RFX3, HIST4H4 and JADE1 that showed continuous downregulation. According to PANTHER, three of the consistently upregulated (ITM2C, FLJ11000, MSMB) and downregulated (HCG9, GAS2L3, FLJ21439) genes, respectively, have not been associated with any biological process or molecular function so far. Thus, these findings revealed interesting new targets for selective elimination of tumor cells and new insights regarding response of tumor cells to alpha-emitter exposure.

SrNp(PO4)2: an original ordered modification of cheralite.

The new compound SrNp(PO(4))(2) (orthorhombic Cmca) has been synthesized by a solid-state reaction and its crystal structure solved ab initio and refined by Rietveld analysis. Though chemically and structurally related to the cheralite CaTh(PO(4))(2), SrNp(PO(4))(2) shows alternate layers of SrO(10) and NpO(8) polyhedra instead of a disordered array of 9-fold polyhedra. Raman and IR spectroscopic measurements also account for ordered cations. This novel structural type allows one to explain the boundaries of the cheralite domain in terms of the cation size and can be proposed as an archetype for a series of other actinide-bearing phosphate compounds.

Synthesis of bimetallic uranium and neptunium complexes of a binucleating macrocycle and determination of the solid-state structure by magnetic analysis.

Syntheses of the bimetallic uranium(III) and neptunium(III) complexes [(UI)(2)(L)], [(NpI)(2)(L)], and [{U(BH(4))}(2)(L)] of the Schiff-base pyrrole macrocycles L are described. In the absence of single-crystal structural data, fitting of the variable-temperature solid-state magnetic data allows the prediction of polymeric structures for these compounds in the solid state.