Stable and high-yielding intrinsic (59) Fe-radiolabeling of the intravenous iron preparations Monofer and Cosmofer.

Commercial iron supplements Monofer(®) and Cosmofer(®) were intrinsically radiolabeled with (59) Fe for the purpose of tracing iron absorption in vivo. Optimized procedures aimed at introducing (59) Fe into the macromolecular construct in a form that was as chemically equivalent to the matrix iron as possible. This was determined by challenging the labeled constructs with diethylenetriaminepentaacetic acid (DTPA) followed by separation by size-exclusion and measurements of radioactivity and iron in the eluted fractions. The final procedures were simple and involved heating aqueous dispersions of the supplements in the presence of [(59) Fe]FeCl3 for 24 h at 95 °C for Monofer, and 85 °C for Cosmofer, resulting in radiochemical yields greater than 94%. High performance size exclusion chromatography, UV-VIS spectroscopy, and dynamic light scattering were used to show that the supplements remained unchanged after radiolabeling, underscoring the applicability of the methodology for radiolabeling commercial iron preparations.

Sensitivity and accuracy of organic matrix-assisted laser desorption and ionisation mass spectrometry of FeCl3 is higher than in in matrix-free approach.

We compare the quality and reliability of laser desorption and ionisation mass spectra of FeCl3 acquired without the assistance of the matrix with the spectra acquired with different organic matrix molecules. Generally, inorganic salts tend to form clusters upon laser irradiation, the signals of which can be easily distinguished from ions arising from the matrix. In the presence of a matrix, cluster ions are, however, mostly suppressed. We have compared the number of analyte signals, accuracy of determination of isotope composition of the analyte and the sensitivity of FeCl3 detection between different approaches. The results obtained imply that the sensitivity of mass spectrometric analysis of FeCl3 is somewhat higher when matrices are applied than in the matrix-free approach. Among all matrices tested in this work, F20TPP seems to be the most promising for further applications as a matrix for mass spectrometry of inorganic salts.

Comparative study of core- and surface-radiolabeling strategies for the assembly of iron oxide nanoparticle-based theranostic nanocomposites.

This work highlights the superiority of the surface-radiolabeling strategy over the core-labeling strategy in the assembly of radioactive iron oxide nanoparticle (IONP)-based nanocomposites for use in multimodal imaging and targeted therapy. It also implies a possible overestimation of the labeling stability in previous studies and points out directions for further optimization.

The energy response of a T.P.A. Mk-II ionization chamber using GEANT4 Monte Carlo simulation.

The low energy model of the GEANT4 Monte Carlo toolkit was used to simulate the energy response of a T.P.A. Mk-II ionization chamber under a variety of different conditions. The sample position resulting in the maximum response along the axial direction of the chamber was obtained. The parameters of the simulation were chosen to account for the maximum effect of the particle backscattering and the setting of most suitable values for the production thresholds and the energy cuts in the GEANT4 Monte Carlo code. The chamber response for different compositions of detector elements was also studied. The simulated radioactive source was a glass ampoule containing 3.6 ml of the radionuclide in an aqueous solution. The energy response of the chamber at the maximum response was obtained for simulations for (60)Co, (22)Na and (59)Fe nuclides. Verification of the simulated response was obtained using experimental measurements with radioactive sources. The simulated results were in good agreement with the experimentally measured data to within 0.04-2.0%. In the energy range below 200 keV the response curve was complex due to the increase of photoelectric cross sections of the chamber materials. Effects due to backscattering occur at boundaries between chamber elements and also become significant at sites of lead shielding at photon energies above 700 keV. The chamber response for different compositions of detector elements was also studied. The response of the chamber depended highly on the energies of emitting particles, source position and materials used in electrodes and thimble wall.

The LSC efficiency for low-Z electron-capture nuclides.

In this paper, we apply the CIEMAT/NIST method to the three low-Z electron-capture nuclides 54Mn, 55Fe and 65Zn by using the KLM and KL1L2L3M atomic rearrangement models, respectively. The counting efficiencies are computed with the new code EMILIA, which comprises an improved model for the interaction of low-energy X-rays with the scintillation cocktail. The calculated counting efficiencies are compared with experimental results.

Half-life measurement of 55Fe.

The half-life of 55Fe was determined experimentally and compared with literature values. A solid 55Fe source was prepared by electrodeposition and repeatedly measured in an X-ray detector at a constant, low solid angle. In total, more than six hundred measurements were performed over a period of ten months, corresponding to one third of the half-life. The experimental method and the corresponding uncertainty budget are presented. The result of 1005.2+/-1.4 days is slightly higher than the current recommended values.

Decay Data Evaluation Project: Evaluation of (52)Fe nuclear decay data.

Within the Decay Data Evaluation Project (DDEP) and the IAEA Coordinated Research Project no. F41029, the evaluation of the nuclear decay data of (52)Fe, a radionuclide of interest in nuclear medicine, was performed. The main nuclear decay data evaluated are: the half-life, decay energy, energies and probabilities of the electron capture and ß(+) transitions, internal conversion coefficients and gamma-ray energies and emission intensities. This new evaluation, made using the DDEP methodology and tools, was included in the DDEP database NUCLEIDE.

Vibrational and 57Fe-Mössbauer spectra of some mixed cation diphosphates of the type M(II)Fe2(III)(P2O7)2.

The infrared (IR), Raman and 57Fe-Mössbauer spectra of SrFe2(P2O7)2, BaFe2(P2O7)2 and PbFe2(P2O7)2 were recorded and discussed on the basis of the structural peculiarities of the compounds.

Half-life and X-ray emission probabilities of 55Fe.

The X-ray emission probabilities of the Mn-K(alpha) and Mn-K(beta) radiation in the decay of 55Fe were measured with a calibrated Si(Li) spectrometer, resulting in 0.245(7) and 0.0338(9), respectively. A half-life of 1003.5(21) day was measured using the same detector.

Epithermal neutron self-shielding factors in foils for collimated beams.

An epithermal neutron self-shielding factor must be introduced to take into account the absorption of a neutron beam crossing a sample. This factor depends on the geometry and dimension of the sample, as well as on the physical and nuclear properties of the nuclides. On the basis of a dimensionless variable, which includes the relevant characteristics of the sample, universal curves for monoenergetic and 1/E collimated neutron beams are proposed, which enable the determination of the self-shielding factor for isolated resonances of high absorber nuclides.

Reinvestigation of a physiological eluate of the 52Fe/52mMn generator.

We have achieved a significant step forward in the potential application of 52mMn2+ (T1/2 = 0.35 h, beta + = 97%) as a myocardial imaging agent with positron emission tomography (PET) by the introduction of a 5% (physiological) glucose solution as an eluent for the 52Fe/52mMn generator. Our experiments have demonstrated the favourable properties of a glucose solution with minimal breakthrough (< 0.3%) of 52Fe and yields of up to 90% 52mMn2+. Although it has been shown that lower 52Fe breakthrough is attainable using other eluents, due to the short half life of 52Fe (8.27 h) breakthrough up to 1% would not appear to significantly alter the efficacy of the 52mMn eluted with this 5% glucose solution. The primary advantage of this approach lies in its convenience of application, in that a 5% glucose solution may be administered directly into patients thereby circumventing the major problem of non-injectable eluates previously associated with this generator.

Effects of Al substitution and thermal annealing on magnetoelectric Ba0.5Sr1.5Zn2Fe12O22 investigated by the enhancement factor of 57Fe nuclear magnetic resonance.

The magnetoelectric properties of hexaferrite Ba0.5Sr1.5Zn2Fe12O22 are significantly improved by Al substitution and thermal annealing. Measuring the enhancement factor of 57Fe NMR, we found direct microscopic evidence that the magnetic moments of the L and S blocks are rotated by a magnetic field in such a way as to increase the net magnetic moment of a magnetic unit, even after the field is removed. Al substitution makes magnetoelectric property arise easily by suppressing the easy-plane anisotropy. The effect of thermal annealing is to stabilize the multiferroic state by reducing the number of pinning sites and the electron spin fluctuation. The transverse conic structure gradually changes to the alternating longitudinal conic structure where spins fluctuate more severely.

Measurement of 56Fe activity produced in inelastic scattering of neutrons created by cosmic muons in an iron shield.

We report on the study of the intensities of several gamma lines emitted after the inelastic scattering of neutrons in (56)Fe. Neutrons were produced via nuclear processes induced by cosmic muons in the 20tons massive iron cube placed at the Earth's surface and used as a passive shield for the HPGe detector. Relative intensities of detected gamma lines are compared with the results collected in the same iron shield by the use of the (252)Cf neutrons. Assessment against the published data from neutron scattering experiments at energies up to 14MeV is also provided. It allowed us to infer the qualitative information about the average energy of muon-created neutrons in the iron shield.

Uncertainties in 63Ni and 55Fe determinations using liquid scintillation counting methods.

The implementation of (63)Ni and (55)Fe determination methods in an environmental laboratory implies their validation. In this process, the uncertainties related to these methods should be analysed. In this work, the expression of the uncertainty of the results obtained using separation methods followed by liquid scintillation counting is presented. This analysis includes the consideration of uncertainties coming from the different alternatives which these methods use as well as those which are specific to the individual laboratory and the competency of its operators in applying the standard ORISE (Oak Ridge Institute for Science and Education) methods.

A simple and widely applicable method to 59Fe-radiolabel monodisperse superparamagnetic iron oxide nanoparticles for in vivo quantification studies.

A simple, fast, efficient, and widely applicable method to radiolabel the cores of monodisperse superparamagnetic iron oxide nanoparticles (SPIOs) with (59)Fe was developed. These cores can be used as precursors for a variety of functionalized nanodevices. A quality control using filtration techniques, size-exclusion chromatography, chemical degradation methods, transmission electron microscopy, and magnetic resonance imaging showed that the nanoparticles were stably labeled with (59)Fe. Furthermore, the particle structure and the magnetic properties of the SPIOs were unchanged. In a second approach, monodisperse SPIOs stabilized with (14)C-oleic acid were synthesized, and the stability of this shell labeling was studied. In proof of principle experiments, the (59)Fe-SPIOs coated with different shells to make them water-soluble were used to evaluate and compare in vivo pharmacokinetic parameters such as blood half-life. It could also be shown that our radiolabeled SPIOs embedded in recombinant lipoproteins can be used to quantify physiological processes in closer detail than hitherto possible. In vitro and in vivo experiments showed that the (59)Fe label is stable enough to be applied in vivo, whereas the (14)C label is rapidly removed from the iron core and is not adequate for in vivo studies. To obtain meaningful results in in vivo experiments, only (59)Fe-labeled SPIOs should be used.

Quantitative targeted biomarker assay for glycated haemoglobin by multidimensional LC using mass spectrometric detection.

The development of quantitative strategies for targeted biomarker analysis represents an urgent task especially in the field of clinical diagnosis. In this regard, the measurement of glycohaemoglobin (HbA(1c)) in blood has become the most specific way of monitoring long-term glycaemia in diabetic patients. Thus, there is an urgent need for methods that provide accurate and precise HbA(1c) results. A new method for the determination of HbA(1c) in blood samples based on the complementary use of multidimensional liquid chromatography (LC) and elemental (inductively coupled plasma mass spectrometry, ICP-MS) and molecular (electrospray-mass spectrometry, ESI-MS) MS techniques has been developed and validated. Different multidimensional separation possibilities by combining affinity and cation exchange chromatography have been explored for the adequate isolation of HbA(1c), which purity is addressed by ESI-MS. The workflow includes a final quantitative determination of HbA(1c) by elemental (Fe) isotope dilution analysis (IDA) with ICP-MS. For this purpose, the post-column addition of the isotopically labeled iron ((57)Fe) has been used to quantify the eluting Fe-species from the column. The IDA methodology has been validated by analyzing a certified reference material and several samples from patients whose HbA(1c) levels were determined by a standard reference method.

Novel diaroylhydrazine ligands as iron chelators: coordination chemistry and biological activity.

The search for orally effective drugs for the treatment of iron overload disorders is an important goal in improving the health of patients suffering diseases such as beta-thalassemia major. Herein, we report the syntheses and characterization of some new members of a series of N-aroyl-N'-picolinoyl hydrazine chelators (the H2IPH analogs). Both 1:1 and 1:2 Fe(III):L complexes were isolated and the crystal structures of Fe(HPPH)Cl2, Fe(4BBPH)Cl2, Fe(HAPH)(APH) and Fe(H3BBPH)(3BBPH) were determined (H2PPH=N,N'-bis-picolinoyl hydrazine; H2APH=N-4-aminobenzoyl-N'-picolinoyl hydrazine, H23BBPH=N-3-bromobenzoyl-N'-picolinoylhydrazine and H24BBPH=N-(4-bromobenzoyl)-N'-(picolinoyl)hydrazine). In each case, a tridentate N,N,O coordination mode of each chelator with Fe was observed. The Fe(III) complexes of these ligands have been synthesized and their structural, spectroscopic and electrochemical characterization are reported. Five of these new chelators, namely H2BPH (N-(benzoyl)-N'-(picolinoyl)hydrazine), H2TPH (N-(2-thienyl)-N'-(picolinoyl)-hydrazine), H2PPH, H23BBPH and H24BBPH, showed high efficacy at mobilizing 59Fe from cells and inhibiting 59Fe uptake from the serum Fe transport protein, transferrin (Tf). Indeed, their activity was much greater than that found for the chelator in current clinical use, desferrioxamine (DFO), and similar to that observed for the orally active chelator, pyridoxal isonicotinoyl hydrazone (H2PIH). The ability of the chelators to inhibit 59Fe uptake could not be accounted for by direct chelation of 59Fe from 59Fe-Tf. The most effective chelators also showed low antiproliferative activity which was similar to or less than that observed with DFO, which is important in terms of their potential use as agents to treat Fe-overload disease.

Density functional study of the electric hyperfine interactions and the redox-structural correlations in the cofactor of nitrogenase. Analysis of general trends in (57)Fe isomer shifts.

The influence of the interstitial atom, X, discovered in a recent crystallographic study of the MoFe protein of nitrogenase, on the electric hyperfine interactions of (57)Fe has been investigated with density functional theory. A semiempirical theory for the isomer shift, delta, is formulated and applied to the cofactor. The values of delta for the relevant redox states of the cofactor are predicted to be higher in the presence of X than in its absence. The analysis strongly suggests a [Mo(4+)4Fe(2+)3Fe(3+)] oxidation state for the S = 3/2 state M(N). Among C(4-), N(3-), and O(2-), oxide is found to be the least likely candidate for X. The analysis suggests that X should be present in the cofactor states M(OX) and M(R) as well as in the alternative nitrogenases. The calculations of the electric field gradients (EFGs) indicate that the small values for DeltaE(Q) in M(N) result from an extensive cancellation between valence and ligand contributions. X emerges from the analysis of the hyperfine interactions as an ionically bonded species. Its major effect is on the asymmetry parameters for the EFGs at the six equatorial sites, Fe(Eq). A spin-coupling scheme is proposed for the state [Mo(4+)4Fe(2+)3Fe(3+)] that is consistent with the measured (57)Fe A-tensors and DeltaE(Q) values for M(N) and identifies the unique site exhibiting the small A value with the terminal Fe site, Fe(T). The optimized structure of a cofactor model has been calculated for several oxidation states. The study reveals a contraction in the average Fe-Fe distance upon increasing the number of electrons stored in the cluster, in accord with extended X-ray absorption fine structure studies. The reliability of the adopted methodology for predicting redox-structural correlations is tested for cuboidal [4Fe-4S] clusters. The calculations reveal a systematic increase in the S...S sulfide distances, in quantitative agreement with the available data. These trends are rationalized by a simple electrostatic model.

Influence of electron donor/acceptor concentrations on hydrous ferric oxide (HFO) bioreduction.

Dissimilatory metal-reducing bacteria (DMRB) facilitate the reduction of Fe and Mn oxides in anoxic soils and sediments and play an important role in the cycling of these metals and other elements such as carbon in aqueous environments. Previous studies investigating the reduction of Fe(III) oxides by DMRB focused on reactions under constant initial electron donor (lactate) and electron acceptor (Fe oxide) concentrations. Because the concentrations of these reactants can vary greatly in the environment and would be expected to influence the rate and extent of oxide reduction, the influence of variable electron acceptor and donor concentrations on hydrous ferric oxide (HFO) bioreduction was investigated. Batch experiments were conducted in pH 7 HCO3 buffered media using Shewanella putrefaciens strain CN32. In general, the rate of Fe(III) reduction decreased with increasing HFO:lactate ratios, resulting in a relatively greater proportion of crystalline Fe(III) oxides of relatively low availability for DMRB. HFO was transformed to a variety of crystalline minerals including goethite, lepidocrocite, and siderite but was almost completely dissolved at high lactate to HFO ratios. These results indicate that electron donor and acceptor concentrations can greatly impact the bioreduction of HFO and the suite of Fe minerals formed as a result of reduction. The respiration driven rate of Fe(II) formation from HFO is believed to be a primary factor governing the array of ferrous and ferric iron phases formed during reduction.