Vergleichende Untersuchung der endokrinen Ophthalmopathie mittels Ultrasonographie, Computertomographie und Fischbioassay

Bei 35 Patienten mit endokriner Ophthalmopathie (eO) wurde zu den Parametern der Schilddrüsenfunktion (T3, T4, TBI, TRH-Test), dem Szintigramm und der Bestimmung der Schilddrüsenantikörper ergänzend die Ultrasonographie (A-scan) und Computertomographie (CT) der Orbita, sowie der Nachweis exophthalmogener Serumaktivität im Fischbioassay durchgeführt. Charakteristische Sonogramme für eine eO fanden sich in 26 Fällen. Die CT ergab bei 24 von 33 Patienten die Verdickung der musculi recti mediales und/oder der musculi recti laterales, sowie bei 17 Patienten eine Verdichtung im Bereich der Orbitaspitze. Im retrobulbären Bindegewebe zeigte sich nach Kontrastmittelgabe keine signifikante Dichtezunahme. Mit beiden Verfahren zusammen waren nur bei 2 Patienten die Kriterien einer eO nicht erfüllt. Die exophthalmogene Serumaktivität wurde in der IgG-Fraktion im Fischbioassay nachgewiesen; die Trefferquote war mit 69% relativ hoch. Zur Diagnostik der eO kann jedoch der Fischbioassay nicht empfohlen werden

Presentation of a new magnetic field therapy system for the treatment of human solid tumors with magnetic fluid hyperthermia

Magnetic fluid hyperthermia (MFH) selectively heats up tissue by coupling alternating current (AC) magnetic fields to targeted magnetic fluids, so that boundaries of different conductive tissues do not interfere with power absorption. In this paper, a new AC magnetic field therapy system for clinical application of MFH is described. With optimized magnetic nanoparticle preparations it will be used for target-specific glioblastoma and prostate carcinoma therapy

Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme

Therapy options at the time of recurrence of glioblastoma multiforme are often limited. We investigated whether treatment with a new intratumoral thermotherapy procedure using magnetic nanoparticles improves survival outcome. In a single-arm study in two centers, 66 patients (59 with recurrent glioblastoma) received neuronavigationally controlled intratumoral instillation of an aqueous dispersion of iron-oxide (magnetite) nanoparticles and subsequent heating of the particles in an alternating magnetic field. Treatment was combined with fractionated stereotactic radiotherapy. A median dose of 30 Gy using a fractionation of 5 × 2 Gy/week was applied. The primary study endpoint was overall survival following diagnosis of first tumor recurrence (OS-2), while the secondary endpoint was overall survival after primary tumor diagnosis (OS-1). Survival times were calculated using the Kaplan–Meier method. Analyses were by intention to treat. The median overall survival from diagnosis of the first tumor recurrence among the 59 patients with recurrent glioblastoma was 13.4 months (95% CI: 10.6–16.2 months). Median OS-1 was 23.2 months while the median time interval between primary diagnosis and first tumor recurrence was 8.0 months. Only tumor volume at study entry was significantly correlated with ensuing survival (P < 0.01). No other variables predicting longer survival could be determined. The side effects of the new therapeutic approach were moderate, and no serious complications were observed. Thermotherapy using magnetic nanoparticles in conjunction with a reduced radiation dose is safe and effective and leads to longer OS-2 compared to conventional therapies in the treatment of recurrent glioblastoma

Lock-in thermography as a rapid and reproducible thermal characterization method for magnetic nanoparticles

Lock-in thermography (LIT) is a sensitive imaging technique generally used in engineering and materials science (e.g. detecting defects in composite materials). However, it has recently been expanded for investigating the heating power of nanomaterials, such as superparamagnetic iron oxide nanoparticles (SPIONs). Here we implement LIT as a rapid and reproducible method that can evaluate the heating potential of various sizes of SPIONs under an alternating magnetic field (AMF), as well as the limits of detection for each particle size. SPIONs were synthesized via thermal decomposition and stabilized in water via a ligand transfer process. Thermographic measurements of SPIONs were made by stimulating particles of varying sizes and increasing concentrations under an AMF. Furthermore, a commercially available SPION sample was included as an external reference. While the size dependent heating efficiency of SPIONs has been previously described, our objective was to probe the sensitivity limits of LIT. For certain size regimes it was possible to detect signals at concentrations as low as 0.1 mg Fe/mL. Measuring at different concentrations enabled a linear regression analysis and extrapolation of the limit of detection for different size nanoparticles

Optomagnetic Nanoplatforms for In Situ Controlled Hyperthermia

This is the peer reviewed version of the following article: Ortgies, Dirk H., Teran, Francisco J. Rocha, Uéslen, Cueva, Leonar de la, Salas, Gorka, cabrera, David, Vanetsev, Alexander S., Rähn, Mikhel, Väino,Sammelselg, Orlosvkii, Yurii V. and Jaque, Daneil "Optomagnetic nanoplatforms for in situ controlled hyperthermia" Advances Funtcional Materials 28.11 (2018) which has been published in final form at http://doi.org/10.1002/adfm.201704434. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."Magnetic nanoparticles (M:NPs) are unique agents for in vivo thermal therapies due to their multimodal capacity for efficient heat generation under optical and/or magnetic excitation. Nevertheless, their transfer from laboratory to the clinic is hampered by the absence of thermal feedback and by the influence that external conditions (e.g., agglomeration and biological matrix interactions) have on their heating efficiency. Overcoming these limitations requires, first, the implementation of strategies providing thermal sensing to M:NPs in order to obtain in situ thermal feedback during thermal therapies. At the same time, M:NPs should be modified so that their heating efficiency will be maintained independently of the environment and the added capability for thermometry. In this work, optomagnetic hybrid nanostructures (OMHSs) that simultaneously satisfy these two conditions are presented. Polymeric encapsulation of M:NPs with neodymium-doped nanoparticles results in a hybrid structure capable of subtissue thermal feedback while making the heating efficiency of M:NPs independent of the medium. The potential application of the OMHSs herein developed for fully controlled thermal therapies is demonstrated by an ex vivo endoscope-assisted controlled intracoronary heating experimentThis work was supported by the Spanish Ministry of Economy and Competitiveness under Projects # MAT2016-75362-C3-1-R, # MAT2015-71806-R and # MAT2013-47395-C4-3-R, the Comunidad de Madrid (NANOFRONTMAG-CM, S2013/MIT-2850), and through the Instituto de Salud Carlos III under Project # PI16/00812. This work has also received funding from European Union’s H2020 and FP7 programme (NOCANTHER, GA 685795). D.H.O. is grateful to the Spanish Ministry of Economy and Competitiveness for a Juan de la Cierva scholarship (FJCI-2014-21101) and F.J.T. for a Ramon y Cajal fellowship (RYC-2011-09617). COST Actions CM1403 and TD1402 (RADIOMAG) are also acknowledged. The synthesis and preliminary testing of the fluorescence properties of the LaF3:Nd(3%) NPs was supported by Project # 16-12-10077 of the Russian Science Foundation. Nonfluorescent characterization of the OMHSs was supported by projects IUT2-24 and IUT20-54 of the Estonian Ministry of Education and Researc

The role of dipole interactions in hyperthermia heating colloidal clusters of densely-packed superparamagnetic nanoparticles

This work aims to investigate the influence of inter-particle dipole interactions on hyperthermia heating colloidal clusters of densely-packed Fe3O4 nanoparticles at low field intensity. Emulsion droplet solvent evaporation method was used to assemble oleic acid modified Fe3O4 particles into compact clusters which were stabilized by surfactant in water. Both experimental and simulation works were conducted to study their heating performance at different cluster’s sizes. The dipole interactions improve the heating only when the clusters are small enough to bring an enhancement in clusters’ shape anisotropy. The shape anisotropy is reduced at greater clusters’ sizes, since the shapes of the clusters become more and more spherical. Consequently, the dipole interactions change to impair the heating efficiency at larger sizes. When the clusters are totally isotropic in shape, the heating efficiency is lower than that of non-interacting particles despite the cluster’s size, although the efficiency increases by a little bit at a particular size most likely due to the dipole couplings. In these situations, one has to use particles with higher magnetic anisotropy and/or saturation magnetization to improve the heating

Particle interactions in liquid magnetic colloids by zero field cooled measurements: effects on heating efficiency

The influence of magnetic interactions in assemblies formed by either aggregated or disaggregated uniform gamma-Fe_2O_3 particles are investigated as a function of particle size, concentration, and applied field. Hyperthermia and magnetization measurements are performed in the liquid phase of colloids consisting of 8 and 13 nm uniform gamma-Fe_2O_3 particles dispersed in water and hexane. Although hexane allows the disagglomerated obtaining particle system; aggregation is observed in the case of water colloids. The zero field cooled (ZFC) curves show a discontinuity in the magnetization values associated with the melting points of water and hexane. Additionally, for 13 nm gamma-Fe_2O_3 dispersed in hexane, a second magnetization jump is observed that depends on particle concentration and shifts toward lower temperature by increasing applied field. This second jump is related to the strength of the magnetic interactions as it is only present in disagglomerated particle systems with the largest size, i.e., is not observed for 8 nm superparamagnetic particles, and surface effects can be discarded. The specific absorption rate (SAR) decreases with increasing concentration only for the hexane colloid, whereas for aqueous colloids, the SAR is almost independent of particle concentration. Our results suggest that, as a consequence of the magnetic interactions, the dipolar field acting on large particles increases with concentration, leading to a decrease of the SAR

Learning form Nature to improve the heat generation of iron-oxide nanoparticles for magnetic hyperthermia applications.

The performance of magnetic nanoparticles is intimately entwined with their structure, mean size and magnetic anisotropy. Besides, ensembles offer a unique way of engineering the magnetic response by modifying the strength of the dipolar interactions between particles. Here we report on an experimental and theoretical analysis of magnetic hyperthermia, a rapidly developing technique in medical research and oncology. Experimentally, we demonstrate that single-domain cubic iron oxide particles resembling bacterial magnetosomes have superior magnetic heating efficiency compared to spherical particles of similar sizes. Monte Carlo simulations at the atomic level corroborate the larger anisotropy of the cubic particles in comparison with the spherical ones, thus evidencing the beneficial role of surface anisotropy in the improved heating power. Moreover we establish a quantitative link between the particle assembling, the interactions and the heating properties. This knowledge opens new perspectives for improved hyperthermia, an alternative to conventional cancer therapies