Combining magnetic hyperthermia and dual T1/T2 MR imaging using highly versatile iron oxide nanoparticles

[EN] Magnetic hyperthermia and magnetic resonance imaging (MRI) are two of the most important biomedical applications of magnetic nanoparticles (MNPs). However, the design of MNPs with good heating performance for hyperthermia and dual T1/T2 contrast for MRI remains a considerable challenge. In this work, ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) are synthesized through a simple one-step methodology. A post-synthetic purification strategy has been implemented in order to separate discrete nanoparticles from aggregates and unstable nanoparticles, leading to USPIONs that preserve chemical and colloidal stability for extended periods of time. The optimized nanoparticles exhibit high saturation magnetization and show good heating efficiency in magnetic hyperthermia experiments. Remarkably, the evaluation of the USPIONs as MRI contrast agents revealed that the nanoparticles are also able to provide significant dual T1/T2 signal enhancement. These promising results demonstrate that USPIONs are excellent candidates for the development of theranostic nanodevices with potential application in both hyperthermia and dual T1/T2 MR imaging.We are grateful to the Spanish Government (projects MAT2015-64139-C4-1-R and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (Projects PROMETEO/2018/024 and PROMETEOII/2014/047) for financial support. S. S. C. is grateful to the Spanish MEC for his FPU grant. JG acknowledges funding from FCT and the ERDF through NORTE2020 through the project Self-reporting immunestimulating formulation for on-demand cancer therapy with real-time treatment response monitoring (028052).Sánchez-Cabezas, S.; Montes-Robles, R.; Gallo, J.; Sancenón Galarza, F.; Martínez-Máñez, R. (2019). Combining magnetic hyperthermia and dual T1/T2 MR imaging using highly versatile iron oxide nanoparticles. Dalton Transactions. 48(12):3883-3892. https://doi.org/10.1039/c8dt04685aS388338924812Lee, J.-H., Jang, J., Choi, J., Moon, S. H., Noh, S., Kim, J., … Cheon, J. (2011). Exchange-coupled magnetic nanoparticles for efficient heat induction. Nature Nanotechnology, 6(7), 418-422. doi:10.1038/nnano.2011.95Hauser, A. K., Wydra, R. J., Stocke, N. A., Anderson, K. W., & Hilt, J. Z. (2015). Magnetic nanoparticles and nanocomposites for remote controlled therapies. Journal of Controlled Release, 219, 76-94. doi:10.1016/j.jconrel.2015.09.039González, B., Ruiz-Hernández, E., Feito, M. J., López de Laorden, C., Arcos, D., Ramírez-Santillán, C., … Vallet-Regí, M. (2011). Covalently bonded dendrimer-maghemite nanosystems: nonviral vectors for in vitro gene magnetofection. Journal of Materials Chemistry, 21(12), 4598. doi:10.1039/c0jm03526bGallo, J., Long, N. J., & Aboagye, E. O. (2013). Magnetic nanoparticles as contrast agents in the diagnosis and treatment of cancer. Chemical Society Reviews, 42(19), 7816. doi:10.1039/c3cs60149hBoyer, C., Whittaker, M. R., Bulmus, V., Liu, J., & Davis, T. P. (2010). The design and utility of polymer-stabilized iron-oxide nanoparticles for nanomedicine applications. NPG Asia Materials, 2(1), 23-30. doi:10.1038/asiamat.2010.6Wáng, Y. X. J., & Idée, J.-M. (2017). A comprehensive literatures update of clinical researches of superparamagnetic resonance iron oxide nanoparticles for magnetic resonance imaging. Quantitative Imaging in Medicine and Surgery, 7(1), 88-122. doi:10.21037/qims.2017.02.09Blanco-Andujar, C., Walter, A., Cotin, G., Bordeianu, C., Mertz, D., Felder-Flesch, D., & Begin-Colin, S. (2016). Design of iron oxide-based nanoparticles for MRI and magnetic hyperthermia. Nanomedicine, 11(14), 1889-1910. doi:10.2217/nnm-2016-5001Shin, T.-H., Choi, Y., Kim, S., & Cheon, J. (2015). Recent advances in magnetic nanoparticle-based multi-modal imaging. Chemical Society Reviews, 44(14), 4501-4516. doi:10.1039/c4cs00345dBusquets, M. A., Estelrich, J., & Sánchez-Martín, M. J. (2015). Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents. International Journal of Nanomedicine, 1727. doi:10.2147/ijn.s76501Lee, N., & Hyeon, T. (2012). Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents. Chem. Soc. Rev., 41(7), 2575-2589. doi:10.1039/c1cs15248cWang, G., Zhang, X., Skallberg, A., Liu, Y., Hu, Z., Mei, X., & Uvdal, K. (2014). One-step synthesis of water-dispersible ultra-small Fe3O4 nanoparticles as contrast agents for T1 and T2 magnetic resonance imaging. Nanoscale, 6(5), 2953. doi:10.1039/c3nr05550gKim, B. H., Lee, N., Kim, H., An, K., Park, Y. I., Choi, Y., … Hyeon, T. (2011). Large-Scale Synthesis of Uniform and Extremely Small-Sized Iron Oxide Nanoparticles for High-ResolutionT1Magnetic Resonance Imaging Contrast Agents. Journal of the American Chemical Society, 133(32), 12624-12631. doi:10.1021/ja203340uNegussie, A. H., Yarmolenko, P. S., Partanen, A., Ranjan, A., Jacobs, G., Woods, D., … Dreher, M. R. (2011). Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound. International Journal of Hyperthermia, 27(2), 140-155. doi:10.3109/02656736.2010.528140Hervault, A., & Thanh, N. T. K. (2014). Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer. Nanoscale, 6(20), 11553-11573. doi:10.1039/c4nr03482aKumar, C. S. S. R., & Mohammad, F. (2011). Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. Advanced Drug Delivery Reviews, 63(9), 789-808. doi:10.1016/j.addr.2011.03.008Deatsch, A. E., & Evans, B. A. (2014). Heating efficiency in magnetic nanoparticle hyperthermia. Journal of Magnetism and Magnetic Materials, 354, 163-172. doi:10.1016/j.jmmm.2013.11.006Zhang, J., Li, X., Rosenholm, J. M., & Gu, H. (2011). Synthesis and characterization of pore size-tunable magnetic mesoporous silica nanoparticles. Journal of Colloid and Interface Science, 361(1), 16-24. doi:10.1016/j.jcis.2011.05.038COROT, C., ROBERT, P., IDEE, J., & PORT, M. (2006). Recent advances in iron oxide nanocrystal technology for medical imaging☆. Advanced Drug Delivery Reviews, 58(14), 1471-1504. doi:10.1016/j.addr.2006.09.013Gonzales, M., Mitsumori, L. M., Kushleika, J. V., Rosenfeld, M. E., & Krishnan, K. M. (2010). Cytotoxicity of iron oxide nanoparticles made from the thermal decomposition of organometallics and aqueous phase transfer with Pluronic F127. Contrast Media & Molecular Imaging, 5(5), 286-293. doi:10.1002/cmmi.391Laurent, S., Forge, D., Port, M., Roch, A., Robic, C., Vander Elst, L., & Muller, R. N. (2008). Magnetic Iron Oxide Nanoparticles: Synthesis, Stabilization, Vectorization, Physicochemical Characterizations, and Biological Applications. Chemical Reviews, 108(6), 2064-2110. doi:10.1021/cr068445eKiss, L. B., Söderlund, J., Niklasson, G. A., & Granqvist, C. G. (1999). New approach to the origin of lognormal size distributions of nanoparticles. Nanotechnology, 10(1), 25-28. doi:10.1088/0957-4484/10/1/006De Palma, R., Peeters, S., Van Bael, M. J., Van den Rul, H., Bonroy, K., Laureyn, W., … Maes, G. (2007). Silane Ligand Exchange to Make Hydrophobic Superparamagnetic Nanoparticles Water-Dispersible. Chemistry of Materials, 19(7), 1821-1831. doi:10.1021/cm0628000Roonasi, P., & Holmgren, A. (2009). A Fourier transform infrared (FTIR) and thermogravimetric analysis (TGA) study of oleate adsorbed on magnetite nano-particle surface. Applied Surface Science, 255(11), 5891-5895. doi:10.1016/j.apsusc.2009.01.031Yan, K., Li, H., Wang, X., Yi, C., Zhang, Q., Xu, Z., … Whittaker, A. K. (2014). Self-assembled magnetic luminescent hybrid micelles containing rare earth Eu for dual-modality MR and optical imaging. J. Mater. Chem. B, 2(5), 546-555. doi:10.1039/c3tb21381aGarland, E. R., Rosen, E. P., Clarke, L. I., & Baer, T. (2008). Structure of submonolayer oleic acid coverages on inorganic aerosol particles: evidence of island formation. Physical Chemistry Chemical Physics, 10(21), 3156. doi:10.1039/b718013fSmolensky, E. D., Park, H.-Y. E., Zhou, Y., Rolla, G. A., Marjańska, M., Botta, M., & Pierre, V. C. (2013). Scaling laws at the nanosize: the effect of particle size and shape on the magnetism and relaxivity of iron oxide nanoparticle contrast agents. Journal of Materials Chemistry B, 1(22), 2818. doi:10.1039/c3tb00369hKodama, R. . (1999). Magnetic nanoparticles. Journal of Magnetism and Magnetic Materials, 200(1-3), 359-372. doi:10.1016/s0304-8853(99)00347-9Bean, C. P., & Livingston, J. D. (1959). Superparamagnetism. Journal of Applied Physics, 30(4), S120-S129. doi:10.1063/1.2185850Li, Q., Kartikowati, C. W., Horie, S., Ogi, T., Iwaki, T., & Okuyama, K. (2017). Correlation between particle size/domain structure and magnetic properties of highly crystalline Fe3O4 nanoparticles. Scientific Reports, 7(1). doi:10.1038/s41598-017-09897-5Roca, A. G., Morales, M. P., O’Grady, K., & Serna, C. J. (2006). Structural and magnetic properties of uniform magnetite nanoparticles prepared by high temperature decomposition of organic precursors. Nanotechnology, 17(11), 2783-2788. doi:10.1088/0957-4484/17/11/010Coey, J. M. D. (1971). Noncollinear Spin Arrangement in Ultrafine Ferrimagnetic Crystallites. Physical Review Letters, 27(17), 1140-1142. doi:10.1103/physrevlett.27.1140Linderoth, S., Hendriksen, P. V., Bo/dker, F., Wells, S., Davies, K., Charles, S. W., & Mo/rup, S. (1994). On spin‐canting in maghemite particles. Journal of Applied Physics, 75(10), 6583-6585. doi:10.1063/1.356902Daou, T. J., Grenèche, J. M., Pourroy, G., Buathong, S., Derory, A., Ulhaq-Bouillet, C., … Begin-Colin, S. (2008). Coupling Agent Effect on Magnetic Properties of Functionalized Magnetite-Based Nanoparticles. Chemistry of Materials, 20(18), 5869-5875. doi:10.1021/cm801405nSerna, C. J., Bødker, F., Mørup, S., Morales, M. P., Sandiumenge, F., & Veintemillas-Verdaguer, S. (2001). Spin frustration in maghemite nanoparticles. Solid State Communications, 118(9), 437-440. doi:10.1016/s0038-1098(01)00150-8Laurent, S., Dutz, S., Häfeli, U. O., & Mahmoudi, M. (2011). Magnetic fluid hyperthermia: Focus on superparamagnetic iron oxide nanoparticles. Advances in Colloid and Interface Science, 166(1-2), 8-23. doi:10.1016/j.cis.2011.04.003N. T. Thanh , Magnetic Nanoparticles From Fabrication to Clinical Applications , CRC Press , Boca Raton , 2012Hergt, R., & Dutz, S. (2007). Magnetic particle hyperthermia—biophysical limitations of a visionary tumour therapy. Journal of Magnetism and Magnetic Materials, 311(1), 187-192. doi:10.1016/j.jmmm.2006.10.1156Dong-Hyun Kim, Thai, Y. T., Nikles, D. E., & Brazel, C. S. (2009). Heating of Aqueous Dispersions Containing ${\hbox{MnFe}}_{2}{\hbox{O}}_{4}$ Nanoparticles by Radio-Frequency Magnetic Field Induction. IEEE Transactions on Magnetics, 45(1), 64-70. doi:10.1109/tmag.2008.2005329Rosensweig, R. E. (2002). Heating magnetic fluid with alternating magnetic field. Journal of Magnetism and Magnetic Materials, 252, 370-374. doi:10.1016/s0304-8853(02)00706-0D. Ortega and Q. A.Pankhurst , in Nanoscience: Volume 1: Nanostructures through Chemistry , ed. P. O'Brien , The Royal Society of Chemistry , Cambridge , 2013 , vol. 1 , pp. 60–88Wildeboer, R. R., Southern, P., & Pankhurst, Q. A. (2014). On the reliable measurement of specific absorption rates and intrinsic loss parameters in magnetic hyperthermia materials. Journal of Physics D: Applied Physics, 47(49), 495003. doi:10.1088/0022-3727/47/49/495003Guibert, C., Dupuis, V., Peyre, V., & Fresnais, J. (2015). Hyperthermia of Magnetic Nanoparticles: Experimental Study of the Role of Aggregation. The Journal of Physical Chemistry C, 119(50), 28148-28154. doi:10.1021/acs.jpcc.5b07796Henoumont, C., Laurent, S., & Vander Elst, L. (2009). How to perform accurate and reliable measurements of longitudinal and transverse relaxation times of MRI contrast media in aqueous solutions. Contrast Media & Molecular Imaging, 4(6), 312-321. doi:10.1002/cmmi.294Biju, S., Gallo, J., Bañobre‐López, M., Manshian, B. B., Soenen, S. J., Himmelreich, U., … Parac‐Vogt, T. N. (2018). A Magnetic Chameleon: Biocompatible Lanthanide Fluoride Nanoparticles with Magnetic Field Dependent Tunable Contrast Properties as a Versatile Contrast Agent for Low to Ultrahigh Field MRI and Optical Imaging in Biological Window. Chemistry – A European Journal, 24(29), 7388-7397. doi:10.1002/chem.201800283Rohrer, M., Bauer, H., Mintorovitch, J., Requardt, M., & Weinmann, H.-J. (2005). Comparison of Magnetic Properties of MRI Contrast Media Solutions at Different Magnetic Field Strengths. Investigative Radiology, 40(11), 715-724. doi:10.1097/01.rli.0000184756.66360.d3Guldris, N., Argibay, B., Kolen’ko, Y. V., Carbó-Argibay, E., Sobrino, T., Campos, F., … Rivas, J. (2016). Influence of the separation procedure on the properties of magnetic nanoparticles: Gaining in vitro stability and T1–T2 magnetic resonance imaging performance. Journal of Colloid and Interface Science, 472, 229-236. doi:10.1016/j.jcis.2016.03.040Hu, F., & Zhao, Y. S. (2012). Inorganic nanoparticle-based T1 and T1/T2 magnetic resonance contrast probes. Nanoscale, 4(20), 6235. doi:10.1039/c2nr31865bDaldrup-Link, H. E. (2017). Ten Things You Might Not Know about Iron Oxide Nanoparticles. Radiology, 284(3), 616-629. doi:10.1148/radiol.2017162759Hu, F., Jia, Q., Li, Y., & Gao, M. (2011). Facile synthesis of ultrasmall PEGylated iron oxide nanoparticles for dual-contrastT1- andT2-weighted magnetic resonance imaging. Nanotechnology, 22(24), 245604. doi:10.1088/0957-4484/22/24/245604Tegafaw, T., Xu, W., Ahmad, M. W., Baeck, J. S., Chang, Y., Bae, J. E., … Lee, G. H. (2015). Dual-modeT1andT2magnetic resonance imaging contrast agent based on ultrasmall mixed gadolinium-dysprosium oxide nanoparticles: synthesis, characterization, andin vivoapplication. Nanotechnology, 26(36), 365102. doi:10.1088/0957-4484/26/36/365102Im, G. H., Kim, S. M., Lee, D.-G., Lee, W. J., Lee, J. H., & Lee, I. S. (2013). Fe3O4/MnO hybrid nanocrystals as a dual contrast agent for both T1- and T2-weighted liver MRI. Biomaterials, 34(8), 2069-2076. doi:10.1016/j.biomaterials.2012.11.05

Sound quality evaluation of floor impact noise generated by walking

Foot step noise is one of the most irritating noises in lightweight timber houses which are commonly in use in Sweden. Since irritating noise can cause stress and discomfort and has a great influence on human well-being and performance, a study was conducted on floor impact sound generated by walking, with the following objectives: - To evaluate the effects of following four factors -floor, ceiling, shoes and weight of walkers- on subjective perception and judgment of annoyance - To build a model based on the psychoacoustic descriptors and subjective judgment of annoyance. Two experiments were carried out using headphones and loudspeakers. The first experiment included 24 sounds, using 3x2x2x2 factorial design and comprising the “floor” at 3 levels and the other three factors (“ceiling”, “shoes” and “weight” of the walker), each at 2 levels. In this experiment headphones and 12 subjects were employed. In experiment 2, the loudspeakers, arranged and processed through cross-talk cancellation were used instead of headphones and 16 sounds (using 2x2x2x2 factorial design) and 12 subjects were selected. Based on the results analysis, the following conclusions were derived: • Loudspeaker seems to be a more suitable tool than headphone to evaluate subjective response to annoyance. • The steel reinforced wooden type of floor when it is associated with unbolted-ceiling (“ceiling off”) has higher annoyance and loudness value. • The role of the 250 Hz octave band seems to be very critical to analyse the floor impact sounds. Nevertheless, all octave bands from 63 to 8000 should be taken into account in order to predict the annoyance response. • The fixed wooden type of floor is the most appropriate type of floor in terms of less annoying when a heavier walker (male walker) is considered. • Walking of a male walker creates higher level impact sounds over all octave bands than female walker. • Specific loudness is the best psychoacoustic descriptor for these sounds.Validerat; 20101217 (root

Adsorption and surface reaction properties of synthesized magnetite nano-particles

The surface chemistry of inorganic materials is of great significance in a number of industrially important processes such as separation of ore by flotation, catalysis, water purification, paper coating and pharmaceutical industry. The purpose of this study has been firsly to develop a method for optimal synthesis of magnetite nanoparticles and secondly to utilize these particles as adsorbent in order to investigate their adsorption/desorption properties. The magnetite nanoparticles were synthesized by coprecipitation of FeCl2 and FeCl3 in alkaline media. The precipitated magnetite was analysed with XRD, TEM and FTIR spectroscopy. For evaluation of the mechanism of magnetite formation via coprecipitation method, iron isotopic measurement was applied and compared with magnetite produced from oxidation of ferrous hydroxide (paper 1). No fractionation of iron isotopes was observed for the magnetite synthesized by coprecipitation, whilst the magnetite formed from ferrous hydroxide showed higher abundance of 54Fe compared to 56Fe in the beginning of the reaction. The synthesized magnetite was coated with a primary layer of oleate and subjected to high temperature in air and argon atmosphere (paper 2).Oleate was selected as a model for Atrac which is a collector used for separation of apatite from magnetite. A combination of thermal analysis and infrared spectroscopy method were used in this study. It was found that calcination of the magnetite-oleate system in air involves oxidation of the double bond of oleate and formation of intermediate oxygen-rich molecules. Thermal decomposition of magnetite coated with a primary layer of oleate under argon atmosphere exhibits two steps weight loss. The first step at ~330oC is associated with oleate desorption/decomposition and an enthalpy change of ÄH = 49.86 J/g. Another weight loss occurs at elevated temperature (740oC) leading to partial reduction of magnetite to wustite and iron. In another work, the synthesized magnetite was deposited over an ATR internal reflection element to study adsorption of carbonate and sulphate anions in-situ. It was concluded from the IR spectra that there are two carbonate species on the surface at pH=8, one tightly bond carbonate as inner sphere complex with monodentate binuclear geometry and the other one is a loosely bond outer-sphere hydrogen bonded carbonate. Adsorption of sulphate was also studied using in-situ ATR spectroscopy (paper 3). Three maxima at 1115, 1044 and 979 cm-1 were observed, based on second derivative spectral method analysis. From the adsorption isotherm, the Langmuir affinity constant, K, was estimated to be 1.2344 x 104 M-1 at pH=4, implying a ∆G0ads= - 33.3 KJ/mol at T= 298oK. The kinetic of adsorption showed an initial fast adsorption especially at higher concentrations, eventually reaching an equilibrium plateau value. The calculated pseudo first order rate constant was (0.09± 0.01) min-1.Godkänd; 2007; 20071123 (ysko

Sorption reactions between ionic species and magnetite in aqueous solution

The surface chemistry of inorganic materials is of great significance in a number of industrially important processes such as separation of ore by flotation, catalysis, water purification, leaching, as well as in the formulation of some pharmaceutical preparations. This thesis deals with magnetite and its sorption properties. Especially it was focused on the sorption of ions present in the process water and possibly affecting the balling properties of the magnetite concentrate in the pelletizing process. It is well-known that these properties become deteriorated if the magnetite surface becomes less hydrophilic, which motivated the use of an amphiphilic adsorbate (sodium oleate) in this study.The magnetite nano-particles were synthesized and subsequently characterized by X-ray, electron microscopy, and infrared spectroscopy. The mechanisms of magnetite formation from co-precipitation of Fe (II) and Fe (III) as well as oxidation of ferrous hydroxide were evaluated using iron isotope fractionation measurements (Paper I).Since magnetite pellets are heated during the sintering process and also may contain small amounts of the hydrophobic collector used in the flotation process, it was interesting to follow what happened with a model collector such as sodium oleate upon heating the magnetite/oleate system. This was studied using a combination of thermal analysis and FTIR spectroscopy. It was found that the oleate molecules were bonded to iron atoms by predominantly a bidentate mononuclear complex and formed essentially a single layer with a distance between the oleate molecules of ~36 Å2. Thermogravimetric analysis showed indicated double bond cleavage that yielded products enriched in oxygen and also capable of forming hydrogen bonds (Paper II).To study how the magnetite surface might be modified caused by process water, the magnetite nano-particles were evenly distributed over an internal reflection element and this combination was used to study the adsorption of ions present in the process water in-situ. The ionic system included the model collector (oleate) in stead of the collector used in practise (Atrac) to separate apatite from magnetite. Among ions in the process water, the adsorption properties of sulphate, silicate, and carbonate were studied as well as the effect of calcium ions on the adsorption properties and the competition between silicate and oleate for the magnetite surface. Paper III focused on the effect of Ca (II) on the adsorption of sulphate and it could be concluded that this effect was of minor importance. On the other hand, calcium ions in solution had a large effect on the adsorption of carbonate ions onto magnetite (Paper VII). During the flotation process, silicate is added to the pulp in order to disperse the magnetite particles and make the reverse flotation of apatite from magnetite more efficient. Accordingly, the adsorption of silicate onto magnetite as well as maghemite was investigated as a function of pH (Papers IV and V). Finally, the kinetics of oleate adsorption onto magnetite and competition between sodium oleate and sodium silicate for the magnetite surface was studied. Of particular interest was to which extent oleate could possibly be substituted for silicate and vice versa. These studies are elaborated in Paper VI.<p>Godkänd; 2009; 20091112 (payroo); DISPUTATION Ämnesområde: Fysikalisk kemi/Physical Chemistry Opponent: Professor Janos Kristof, University of Pannonia, Ungern Ordförande: Docent Allan Holmgren, Luleå tekniska universitet Tid: Måndag den 21 december 2009, kl 13.00 Plats: C 305, Luleå tekniska universitet</p

A study on the mechanism of magnetite formation based on iron isotope fractionation

Having knowledge of mechanism of magnetite formation is essential in a number of industrial processes including magnetite synthesis and corrosion of iron. In this study, magnetite nano-particle was synthesized via two different ways; coprecipitation of iron (II) and (III) and oxidation of ferrous hydroxide. The samples were characterized using X-ray diffraction (XRD), Mid-Far IR spectroscopy, scanning electron microscopy (SEM), chemical analysis for determination of Fe II/Fe III ratio and ICP-MS for iron isotopic ratio (56Fe/54Fe) measurement. Since fractionation of iron isotopes depends on reaction rate and bonding strength, interpretation of the isotopic data with respect to the possible mechanisms is discussed. No fractionation of iron isotopes was observed for the magnetite synthesized by coprecipitation, whilst magnetite formed from ferrous hydroxide showed higher abundance of '4Fe compared to 56Fe in the beginning of reaction, implying the significance of the following reaction: Fe (OH)2 (solid) [Fe (OH)]+(aq) + OH-.Godkänd; 2009; 20090604 (andbra