TY - JOUR A1 - Anderhalten, L. A1 - Silva, R. V. A1 - Morr, A. A1 - Wang, S. A1 - Smorodchenko, A. A1 - Saatz, Jessica A1 - Traub, Heike A1 - Mueller, S. A1 - Boehm-Sturm, P. A1 - Rodriguez-Sillke, Y. A1 - Kunkel, D. A1 - Hahndorf, J. A1 - Paul, F. A1 - Taupitz, M. A1 - Sack, I. A1 - Infante-Duarte, C. T1 - Different Impact of Gadopentetate and Gadobutrol on Inflammation-Promoted Retention and Toxicity of Gadolinium Within the Mouse Brain N2 - Objectives: Using a murine model of multiple sclerosis, we previously showed that repeated administration of gadopentetate dimeglumine led to retention of gadolinium (Gd) within cerebellar structures and that this process was enhanced with inflammation. This study aimed to compare the kinetics and retention profiles of Gd in inflamed and healthy brains after application of the macrocyclic Gd-based contrast agent (GBCA) gadobutrol or the linear GBCA gadopentetate. Moreover, potential Gd-induced neurotoxicity was investigated in living hippocampal slices ex vivo. Materials and Methods: Mice at peak of experimental autoimmune encephalomyelitis (EAE; n = 29) and healthy control mice (HC; n = 24) were exposed to a cumulative dose of 20 mmol/kg bodyweight of either gadopentetate dimeglumine or gadobutrol (8 injections of 2.5 mmol/kg over 10 days). Magnetic resonance imaging (7 T) was performed at baseline as well as at day 1, 10, and 40 post final injection (pfi) of GBCAs. Mice were sacrificed after magnetic resonance imaging and brain and blood Gd content was assessed by laser ablation-inductively coupled plasma (ICP)-mass spectrometry (MS) and ICP-MS, respectively. In addition, using chronic organotypic hippocampal slice cultures, Gd-induced neurotoxicity was addressed in living brain tissue ex vivo, both under control or inflammatory (tumor necrosis factor α [TNF-α] at 50 ng/μL) conditions. Results: Neuroinflammation promoted a significant decrease in T1 relaxation times after multiple injections of both GBCAs as shown by quantitative T1 mapping of EAE brains compared with HC. This corresponded to higher Gd retention within the EAE brains at 1, 10, and 40 days pfi as determined by laser ablation-ICP-MS. In inflamed cerebellum, in particular in the deep cerebellar nuclei (CN), elevated Gd retention was observed until day 40 after last gadopentetate application (CN: EAE vs HC, 55.06 ± 0.16 μM vs 30.44 ± 4.43 μM). In contrast, gadobutrol application led to a rather diffuse Gd content in the inflamed brains, which strongly diminished until day 40 (CN: EAE vs HC, 0.38 ± 0.08 μM vs 0.17 ± 0.03 μM). The analysis of cytotoxic effects of both GBCAs using living brain tissue revealed an elevated cell death rate after incubation with gadopentetate but not gadobutrol at 50 mM. The cytotoxic effect due to gadopentetate increased in the presence of the inflammatory mediator TNF-α (with vs without TNF-α, 3.15% ± 1.18% vs 2.17% ± 1.14%; P = 0.0345). Conclusions: In the EAE model, neuroinflammation promoted increased Gd retention in the brain for both GBCAs. Whereas in the inflamed brains, efficient clearance of macrocyclic gadobutrol during the investigated time period was observed, the Gd retention after application of linear gadopentetate persisted over the entire observational period. Gadopentetate but not gadubutrol appeared to be neurotoxic in an ex vivo paradigm of neuronal inflammation. KW - Imaging KW - ICP-MS KW - Gadolinium KW - Contrast agent KW - Laser ablation KW - Brain KW - Multiple sclerosis PY - 2022 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-546910 DO - https://doi.org/10.1097/RLI.0000000000000884 SN - 0020-9996/22/0000–0000 VL - 57 IS - 10 SP - 677 EP - 688 PB - Wolters Kluwer N.V. CY - Alphen aan den Rijn, The Netherlands AN - OPUS4-54691 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kader, A. A1 - Kaufmann, Jan Ole A1 - Mangarova, D. B. A1 - Moeckel, J. A1 - Brangsch, J. A1 - Adams, L. C. A1 - Zhao, J. A1 - Reimann, C. A1 - Saatz, Jessica A1 - Traub, Heike A1 - Buchholz, R. A1 - Karst, U. A1 - Hamm, B. A1 - Makowski, M. R. T1 - Iron Oxide Nanoparticles for Visualization of Prostate Cancer in MRI N2 - Prostate cancer (PCa) is one of the most common cancers in men. For detection and diagnosis of PCa, non-invasive methods, including magnetic resonance imaging (MRI), can reduce the risk potential of surgical intervention. To explore the molecular characteristics of the tumor, we investigated the applicability of ferumoxytol in PCa in a xenograft mouse model in two different tumor volumes, 500 mm3 and 1000 mm3. Macrophages play a key role in tumor progression, and they are able to internalize iron-oxide particles, such as ferumoxytol. When evaluating T2*-weighted sequences on MRI, a significant decrease of signal intensity between pre- and post-contrast images for each tumor volume (n = 14; p < 0.001) was measured. We, furthermore, observed a higher signal loss for a tumor volume of 500 mm3 than for 1000 mm3. These findings were confirmed by histological examinations and laser ablation inductively coupled plasma-mass spectrometry. The 500 mm3 tumors had 1.5% iron content (n = 14; sigma = 1.1), while the 1000 mm3 tumors contained only 0.4% iron (n = 14; sigma = 0.2). In vivo MRI data demonstrated a correlation with the ex vivo data (R2 = 0.75). The results of elemental analysis by inductively coupled plasma-mass spectrometry correlated strongly with the MRI data (R2 = 0.83) (n = 4). Due to its long retention time in the blood, biodegradability, and low toxicity to patients, ferumoxytol has great potential as a contrast agent for visualization PCa. KW - Imaging KW - Nanoparticle KW - Cancer KW - Iron oxide KW - ICP-MS KW - Magnetic resonance imaging PY - 2022 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-550075 DO - https://doi.org/10.3390/cancers14122909 VL - 14 IS - 12 SP - 1 EP - 13 PB - MDPI CY - Basel, Switzerland AN - OPUS4-55007 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Golusda, L. A1 - Kühl, A. A. A1 - Lehmann, M. A1 - Dahlke, K. A1 - Mueller, S. A1 - Boehm-Sturm, P. A1 - Saatz, Jessica A1 - Traub, Heike A1 - Schnorr, J. A1 - Freise, C. A1 - Taupitz, M. A1 - Biskup, K. A1 - Blanchard, V. A1 - Klein, O. A1 - Sack, I. A1 - Siegmund, B. A1 - Paclik, D. T1 - Visualization of inflammation in experimental colitis by magnetic resonance imaging using very small superparamagnetic iron oxide particles N2 - Inflammatory bowel diseases (IBD) comprise mainly ulcerative colitis (UC) and Crohn´s disease (CD). Both forms present with a chronic inflammation of the (gastro) intestinal tract, which induces excessive changes in the composition of the associated extracellular matrix (ECM). In UC, the inflammation is limited to the colon, whereas it can occur throughout the entire gastrointestinal tract in CD. Tools for early diagnosis of IBD are still very limited and highly invasive and measures for standardized evaluation of structural changes are scarce. To investigate an efficient non-invasive way of diagnosing intestinal inflammation and early changes of the ECM, very small superparamagnetic iron oxide nanoparticles (VSOPs) in magnetic resonance imaging (MRI) were applied in two mouse models of experimental colitis: the dextran sulfate sodium (DSS)-induced colitis and the transfer model of colitis. For further validation of ECM changes and inflammation, tissue sections were analyzed by immunohistochemistry. For in depth ex-vivo investigation of VSOPs localization within the tissue, Europium-doped VSOPs served to visualize the contrast agent by imaging mass cytometry (IMC). VSOPs accumulation in the inflamed colon wall of DSS-induced colitis mice was visualized in T2* weighted MRI scans. Components of the ECM, especially the hyaluronic acid content, were found to influence VSOPs binding. Using IMC, colocalization of VSOPs with macrophages and endothelial cells in colon tissue was shown. In contrast to the DSS model, colonic inflammation could not be visualized with VSOP-enhanced MRI in transfer colitis. VSOPs present a potential contrast agent for contrast-enhanced MRI to detect intestinal inflammation in mice at an early stage and in a less invasive manner depending on hyaluronic acid content. KW - Inflammation KW - Imaging KW - Immunohistochemistry KW - MRI KW - Nanoparticle KW - Extracellular matrix KW - Laser ablation KW - ICP-MS PY - 2022 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-555395 DO - https://doi.org/10.3389/fphys.2022.862212 SN - 1664-042X VL - 13 IS - July 2022 SP - 1 EP - 15 PB - Frontiers Research Foundation CY - Lausanne AN - OPUS4-55539 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Löhr, Konrad A1 - Traub, Heike A1 - Wanka, Antje Jutta A1 - Panne, Ulrich A1 - Jakubowski, Norbert T1 - Quantification of metals in single cells by LA-ICP-MS: Comparison of single spot analysis and imaging N2 - LA-ICP-MS is increasingly used for single cell analysis in two different detection modes using either the imaging mode with subcellular resolution or alternatively single spot analysis of cells with a larger laser spot size. This study compares the analytical figures of merit of both detection modes (signal to noise, precision, accuracy, throughput), as well as ease of operation and data evaluation. Adherent 3T3 fibroblast cells were stained with two metal dyes (mDOTA-Ho, Ir-DNA-intercalator) and several dozen cells were measured using both modes. We found a ten times higher throughput for single spot analysis, which has as well a straightforward data analysis, shortening the total analysis time further. The signal to noise ratio for single spot analysis was found to be slightly better compared to the signal to noise of pixels in imaging. The mean metal intensity per single cell differed by only 10% between both modes and obtained distributions were found to show no statistically significant differences. Using matrix matched calibration based on standards spotted onto nitrocellulose membrane, we achieved detection limits (10s) of 12 fg for Ir and 30 fg for Ho and quantified 57 +/-35 fg Ir and 1192 +/- 707 fg Ho per single cell. Compared to a conventional ICP-MS measurement of a digest of about 60000 cells, 54% of Ir content and 358% Ho content was found using quantitative LA-ICP-MS. The difference might be a consequence of the two metal dyes binding to different structures of the cell and therefore might behave differently in sample preparation for conventional and LA-ICP-MS. KW - Cells KW - Laser ablation KW - ICP-MS KW - Metals KW - Quantification PY - 2018 DO - https://doi.org/10.1039/c8ja00191j SN - 0267-9477 VL - 33 IS - 9 SP - 1579 EP - 1587 PB - RSC Royal Society of Chemistry CY - London AN - OPUS4-46441 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Cruz-Alonso, M. A1 - Fernandez, B. A1 - Alvarez, L. A1 - Gonzalez-Iglesias, H. A1 - Traub, Heike A1 - Jakubowski, Norbert A1 - Pereiro, R. T1 - Bioimaging of metallothioneins in ocular tissue sections by laser ablation-ICP-MS using bioconjugated gold nanoclusters as specific tags N2 - An immunohistochemical method is described to visualize the distribution of metallothioneins 1/2 (MT 1/2) and metallothionein 3 (MT 3) in human ocular tissue. It is making use of (a) antibodies conjugated to gold nanoclusters (AuNCs) acting as labels, and (b) laser ablation (LA) coupled to inductively coupled plasma – mass spectrometry (ICP-MS). Water-soluble fluorescent AuNCs (with an average size of 2.7 nm) were synthesized and then conjugated to antibody by carbodiimide coupling. The surface of the modified AuNCs was then blocked with hydroxylamine to avoid nonspecific interactions with biological tissue. Immunoassays for MT 1/2 and MT 3 in ocular tissue sections (5 μm thick) from two post mortem human donors were performed. Imaging studies were then performed by fluorescence using confocal microscopy, and LA-ICP-MS was performed in the retina to measure the signal for gold. Signal amplification by the >500 gold atoms in each nanocluster allowed the antigens (MT 1/2 and MT 3) to be imaged by LA-ICP-MS using a laser spot size as small as 4 μm. The image patterns found in retina are in good agreement with those obtained by conventional fluorescence immunohistochemistry which was used as an established reference method. KW - Nanocluster KW - Immunohistochemistry KW - Laser ablation KW - ICP-MS KW - Fluorescence KW - Bioimaging PY - 2018 DO - https://doi.org/10.1007/s00604-017-2597-1 SN - 1436-5073 SN - 0026-3672 VL - 185 IS - 1 SP - 64 EP - 72 PB - Springer CY - Vienna AN - OPUS4-44637 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hussein, S. A1 - Kühl, A. A. A1 - Golusda, L. A1 - Plattner, C. A1 - Heinze, N. A1 - Sturm, G. A1 - Freise, C. A1 - Traub, Heike A1 - Schannor, Mathias A1 - Trajanoski, Z. A1 - Taupitz, M. A1 - Siegmund, B. A1 - Paclik, D. T1 - Phenotype and function of human monocytes remain mainly unaffected by very small superparamagnetic iron oxide particles N2 - The field of medical application of organic or inorganic nanoparticles is extensive. Medical nanoparticles offer benefits but pose risks. For safe use in diagnostics and therapy, they should be inert, non-immunogenic, non-aggregating, and avoid long-term accumulation in sensitive tissues like bone marrow or the brain. We have developed in-house very small superparamagnetic iron oxide nanoparticles (VSOP), 7 nm in size, which have been successfully used in preclinical magnetic resonance imaging (MRI) to detect intestinal inflammation, neuroinflammation and atherosclerosis. This study examines nanoparticle effects on human blood cells focusing on monocytes in vitro as a first step toward clinical application. Whole blood and monocytes from healthy donors and patients with inflammatory bowel disease were treated with VSOP in vitro and analyzed for changes in their transcriptome, phenotype and function. RNA sequencing of monocytes identified the transferrin receptor as one of the most significantly downregulated genes after VSOP treatment, likely to limit iron uptake. Whereas whole blood RNA sequencing showed significant changes only in three non-coding genes. CyTOF analysis confirmed that VSOP-treated monocytes remain inactive, with no increased proliferation or altered migration. Metabolically, VSOP uptake enhanced the oxygen consumption rate. This effect was likely due to phagocytosis rather than effects mediated by the VSOP itself, as phagocytosis of latex beads showed comparable results. In summary, the analysis of peripheral blood mononuclear cells and monocytes suggests that VSOP treatment has no major impact on immune cell phenotype or function indicating VSOP as a promising diagnostic tool in MRI for inflammatory bowel disease. KW - Imaging KW - Nanoparticle KW - Monocytes KW - Contrast agent KW - Diagnostics KW - ICP-MS KW - LA-ICP-MS KW - VSOP PY - 2025 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-632012 DO - https://doi.org/10.3389/fnano.2025.1584000 SN - 2673-3013 VL - 7 SP - 1 EP - 16 PB - Frontiers Media CY - Lausanne AN - OPUS4-63201 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Traub, Heike A1 - Wälle, M. A1 - Koch, J. A1 - Panne, Ulrich A1 - Matschat, Ralf A1 - Kipphardt, Heinrich A1 - Günther, D. T1 - Evaluation of different calibration strategies for the analysis of pure copper and zinc samples using femtosecond laser ablation ICP-MS N2 - Solution-doped metal powder pellets as well as aspirated liquids were used as calibration samples to analyze pure copper and zinc certified reference materials (CRMs) by femtosecond laser ablation ICP-MS. It was demonstrated that calibration by copper pellets resulted in relative deviations up to 20%, whereas fs-LA-ICP-MS among copper-based CRMs led to inaccuracies in the same range unless nominal mass fractions were chosen to be <3 mg/kg. Calibration by zinc pellets generally provided better accuracy. Depending on the analyte considered, deviations below 10% were obtained even for mass fractions close to the limit of quantification. Our data, therefore, indicate solution-doped metal powder pellets to be suitable as calibration samples for fs-LA-ICP-MS of metals. Furthermore, the utilization of liquid standards for calibration was found to result in stronger deviations of up to 50% for both copper and zinc samples which, in addition, turned out to be dependent on the plasma conditions. KW - Laser ablation KW - ICP-MS KW - Calibration KW - Copper KW - Zinc KW - Metal PY - 2009 DO - https://doi.org/10.1007/s00216-009-3061-9 SN - 1618-2642 SN - 1618-2650 VL - 395 IS - 5 SP - 1471 EP - 1480 PB - Springer CY - Berlin AN - OPUS4-20402 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Wienold, Julia A1 - Traub, Heike A1 - Bresch, Harald A1 - Seeger, Stefan A1 - Recknagel, Sebastian A1 - Kipphardt, Heinrich T1 - Effort on calibration of infrared spark ablation of copper with synthetic copper standards N2 - Two types of copper samples, compact certified copper reference materials and calibration samples prepared from liquid doped, pressed copper powders, were studied in terms of accuracy of obtained calibration functions originating from infrared spark ablation. Additionally, corresponding particle size distributions of the aerosols from infrared spark ablation were recorded. It is shown that the differences in quantification results, originating from the two sets of calibration functions, could not mainly be ascribed to different particle size distributions of the two copper sample types. Possible other causes, as different ablation rates, parts of melting and differences of the chemical constitutions of the two sample types were explored. KW - Calibration KW - Spark ablation KW - Synthetic standard KW - Particle size distribution KW - Fractionation KW - Laser ablation KW - ICP-MS PY - 2011 DO - https://doi.org/10.1016/j.sab.2011.04.005 SN - 0584-8547 SN - 0038-6987 VL - 66 IS - 6 SP - 432 EP - 438 PB - Elsevier B.V. CY - Amsterdam AN - OPUS4-24065 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Müller, L. A1 - Traub, Heike A1 - Jakubowski, Norbert T1 - Novel applications of lanthanoides as analytical or diagnostic tools in the life sciences by ICP-MS-based techniques N2 - Inductively coupled plasma mass spectrometry (ICP-MS) is a well-established analytical method for multi-elemental analysis in particular for elements at trace and ultra-trace levels. It has found acceptance in various application areas during the last decade. ICP-MS is also more and more applied for detection in the life sciences. For these applications, ICP-MS excels by a high sensitivity, which is independent of the molecular structure of the analyte, a wide linear dynamic range and by excellent multi-element capabilities. Furthermore, methods based on ICP-MS offer simple quantification concepts, for which usually (liquid) standards are applied, low matrix effects compared to other conventional bioanalytical techniques, and relative limits of detection (LODs) in the low pg g−1 range and absolute LODs down to the attomol range. In this chapter, we focus on new applications where the multi-element capability of ICP-MS is used for detection of lanthanoides or rare earth elements, which are applied as elemental stains or tags of biomolecules and in particular of antibodies. KW - ICP-MS KW - Life sciences KW - Mass cytometry KW - Laser ablation (LA)-ICP-MS KW - Bioimaging PY - 2016 DO - https://doi.org/10.1515/psr-2016-0064 SN - 2365-659X SN - 2365-6581 VL - 1 IS - 11 SP - 1 EP - 19 AN - OPUS4-40234 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Drescher, D. A1 - Büchner, T. A1 - Schrade, P. A1 - Traub, Heike A1 - Werner, S. A1 - Guttmann, P. A1 - Bachmann, S. A1 - Kneipp, J. T1 - Influence of Nuclear Localization Sequences on the Intracellular Fate of Gold Nanoparticles N2 - Directing nanoparticles to the nucleus by attachment of nuclear localization sequences (NLS) is an aim in many applications. Gold nanoparticles modified with two different NLS were studied while crossing barriers of intact cells, including uptake, endosomal escape, and nuclear translocation. By imaging of the nanoparticles and by characterization of their molecular interactions with surface-enhanced Raman scattering (SERS), it is shown that nuclear translocation strongly depends on the particular incubation conditions. After an 1 h of incubation followed by a 24 h chase time, 14 nm gold particles carrying an adenoviral NLS are localized in endosomes, in the cytoplasm, and in the nucleus of fibroblast cells. In contrast, the cells display no nanoparticles in the cytoplasm or nucleus when continuously incubated with the nanoparticles for 24 h. The ultrastructural and spectroscopic data indicate different processing of NLS-functionalized particles in endosomes compared to unmodified particles. NLS functionalized nanoparticles form larger intraendosomal aggregates than unmodified gold nanoparticles. SERS spectra of cells with NLS-functionalized gold nanoparticles contain bands assigned to DNA and were clearly different from those with unmodified gold nanoparticles. The different processing in the presence of an NLS is influenced by a continuous exposure of the cells to nanoparticles and an ongoing nanoparticle uptake. This is supported by mass-spectrometry-based quantification that indicates enhanced uptake of NLS-functionalized nanoparticles compared to unmodified particles under the same conditions. The results contribute to the optimization of nanoparticle analysis in cells in a variety of applications, e.g., in theranostics, biotechnology, and bioanalytics. KW - Nanoparticle KW - Laser ablation KW - SERS KW - ICP-MS PY - 2021 DO - https://doi.org/10.1021/acsnano.1c04925 SN - 1936-086X VL - 15 IS - 9 SP - 14838 EP - 14849 PB - American Chemical Society AN - OPUS4-54047 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -