TY - CONF A1 - Traub, Heike T1 - Elemental mapping to study the interaction of MRI contrast agents with extracellular matrix components N2 - Non-specific Gd-based contrast agents (GBCAs) have long been routinely used in clinical magnetic resonance imaging (MRI) diagnostics. Nevertheless, the interaction of such contrast agents with tissue components is not yet fully understood. Typically, they go into extracellular space. The extracellular matrix (ECM) is a three-dimensional network of macromolecules providing structural and biochemical support of the surrounding cells in all mammalian tissues. It is composed of structural proteins (e.g., collagen, elastin) and proteoglycans, which consist of glycosaminoglycans (GAGs) covalently bound to a protein core. GAGs are long, linear polysaccharides composed of repeating disaccharide units that differ in molecular mass, disaccharide structure and degree of sulfation. Many diseases, including inflammation, fibrosis, and tumor invasion, are associated with characteristic ECM changes, especially at an early stage of disease development. As disease severity increases, the amount of one or more different GAG types in the ECM and the extent of GAG sulfation increases. Characteristic of GAGs is their ability to form complexes with cations, e.g., with lanthanides. Thus, GAGs could be a potential binding partner for GBCA molecules as a whole or for dechelated Gd. Currently, there are still many unanswered questions about the interaction of contrast agents with ECM components. In this study, therefore, the uptake and distribution of ionic Gd and various linear and macrocyclic GBCAs was investigated in spheroids as model systems mimicking the complex physiologically relevant tissue microenvironment. Chinese hamster ovary (CHO) cells and CRL-2242 cells, a CHO mutant that does not produce sulfated GAGs, were used to prepare spheroids. Afterwards the spheroids were incubated with gadolinium chloride and GBCAs. For elemental mapping laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) and synchrotron radiation nano X-ray fluorescence spectroscopy (syn-nanoXRF) were used. Although all spheroids were exposed to identical Gd concentrations, differences were observed in the spatial distribution and the amount of Gd taken up. After incubation with linear and macrocyclic GBCAs, Gd is detected in the interior of both types of spheroids. Furthermore, differences in the Gd amount were found depending on the GBCA used. In contrast, incubation with gadolinium chloride leads to an Gd enrichment in the outer regions of the spheroids as well as to much higher Gd contents compared to incubation with GBCAs. Both LA-ICP-TOFMS and syn-nanoXRF can make an important contribution to better understand the relationship between the affinity of GBCAs and ECM components. However, to elucidate such complex interactions, further studies are needed, also with other (bio-)analytical techniques. T2 - Euroanalysis 2025 CY - Barcelona, Spain DA - 31.08.2025 KW - ICP-MS KW - Laser ablation KW - Contrast agent KW - Spheroid KW - Extracellular matrix PY - 2025 AN - OPUS4-64143 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Traub, Heike T1 - Unraveling the interaction of MRI contrast agents with tissue using LA ICP MS N2 - Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is increasingly used to study the distribution of metal-containing drugs, imaging probes and nanomaterials in connection with disease related changes and therapy progress. Additionally, biomolecules can be detected indirectly by using metal-tagged antibodies. The extracellular matrix (ECM) is, besides the cells, an important component of all body tissues. The macromolecular network of the ECM consists of structural proteins (e.g., collagen, elastin) and proteoglycans composed of highly negatively charged carbohydrates, the glycosaminoglycans (GAGs), which are covalently linked to a protein core. Many diseases, including inflammatory processes and tumors, are associated with characteristic ECM changes at an early stage. Recent studies have shown that contrast agents for magnetic resonance imaging (MRI), which are based on gadolinium containing chelate complexes or iron oxide nanoparticles, can bind themselves to ECM components. To elucidate the role of GAGs like keratan sulfate (KS) and its modification state in disease, highly specific tools are necessary. As a complement to conventional immunohistochemistry LA-ICP-MS was applied to investigate the distribution of KS in tissue thin sections using a well characterized anti-KS antibody labelled with metal ions. Furthermore, LA-ICP-MS was used for the detection of MRI contrast agents and the identification of their target cells and molecules in tissue samples from animal models, e.g. for cardiovascular diseases. The results show the possibilities of LA-ICP-MS for the elucidation of pathological tissue changes. T2 - European Workshop on Laser Ablation (EWLA 2022) CY - Berne, Switzerland DA - 12.07.2022 KW - Laser ablation KW - Imaging KW - ICP-MS KW - Antibody PY - 2022 AN - OPUS4-55315 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Traub, Heike T1 - Laser Ablation ICP-ToF-MS to investigate the interaction of MRI contrast agents with extracellular matrix components N2 - Non-specific Gd-based contrast agents (GBCAs) have long been routinely used in clinical magnetic resonance imaging (MRI). However, the interaction of such contrast agents with tissue components is not yet fully understood. Alongside cells, the extracellular matrix (ECM) is an important component of mammalian tissue. It is a three-dimensional network of macromolecules that provides structural and biochemical support to the surrounding cells. Many diseases, including inflammation, fibrosis, and tumour invasion, are associated with characteristic ECM changes. The ECM consists of structural proteins (e.g., collagen, elastin) and proteoglycans, which are composed of glycosaminoglycans (GAGs) covalently linked to a protein core. GAGs are long, linear polysaccharides consisting of repeated disaccharide units widely varying in molecular mass, disaccharide structure, and sulfation degree. Characteristic of GAGs is their ability to form complexes with cations such as lanthanides. Thus, GAGs could be a potential binding partner for GBCA molecules as a whole or for dechelated Gd. Currently, there are still many unanswered questions about the interaction of contrast agents with ECM components. This study therefore investigated the uptake and distribution of different GBCAs in spheroids that mimic biological tissue and have different ECM expressions. Chinese hamster ovary (CHO) cells and GAG-depleted CRL-2242 cells were used to prepare spheroids. These were then incubated for several minutes with gadolinium chloride and various linear and macrocyclic GBCAs. Cryosections of the spheroids were used for imaging measurements with a low-dispersion laser ablation system coupled to an inductively coupled plasma time-of-flight mass spectrometer (LA/ICP-ToF-MS). Gelatine doped with multi-element solutions was used for matrix-matched quantification of Gd and other relevant elements such as Cu, Fe and Zn. Although all spheroids were incubated with identical Gd concentrations, significant differences in the amount of Gd taken up were observed. Gadolinium chloride is absorbed more strongly than the contrast agents and accumulates mainly in the outer regions of the spheroids. In contrast, after incubation with the linear and macrocyclic contrast agents, Gd is detected in the interior of both types of spheroids. T2 - European Workshop on Laser Ablation, EWLA 2024 CY - Ghent, Belgium DA - 02.07.2024 KW - ICP-MS KW - Laser ablation KW - Spheroid KW - Contrast agent PY - 2024 AN - OPUS4-60575 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -