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01 februari 2023, Item does not contain fulltext, Background The use of gadolinium-based contrast agents (GBCAs) is linked to gadolinium retention in the skeleton of healthy individuals. The mechanism of gadolinium incorporation into bone tissue is not fully understood and requires spatially resolved analysis to locate the gadolinium. Purpose To compare the quantitative distribution of gadolinium retained over time in rodent femur following the administration of gadodiamide and gadobutrol at three different time points. Materials and Methods In this animal study conducted between May 2018 and April 2020, 108 9-week-old healthy rats were repeatedly injected with either gadodiamide, gadobutrol, or saline solution and were killed 1, 3, or 12 months after the last injection. The femurs of six female and six male rats per each group and time point were collected. Quantitative elemental imaging of gadolinium in longitudinal thin sections was performed on one sample per sex with use of laser ablation inductively coupled plasma mass spectrometry (ICP-MS). Gadolinium concentration was determined with use of ICP-MS on the samples of all animals (six per group). Mann-Whitney U tests were applied on pairwise comparisons to determine potential sex effect and GBCA effect on gadolinium concentrations. Results The highest gadolinium retention was observed in the gadodiamide group (concentration, 97-200 nmol · g(-1)), exceeding the mean concentration in the gadobutrol group (6.5-17 nmol · g(-1)). However, the gadolinium distribution pattern was similar for both contrast agents, showing prominent gadolinium retention at endosteal surfaces, in the bone marrow, and in small tissue pores. Gadolinium distribution in cortical bone changed over time, initially showing a thin rim of higher concentration close to the periosteum, which appeared to grow wider and move toward the interior of the femur over 1 year. Conclusion For both gadolinium-based contrast agents, gadolinium retention in rat bone was initially located close to the periosteu

Innovation in mass spectrometry (MS) and the rapidly increasing throughput and sensitivity of MS instrumentation require adaptations and innovations in data processing tools. Here, we introduce MZmine 3, a scalable MS data analysis platform that supports hybrid datasets from various instrumental setups, including liquid and gas chromatography (LC and GC)–MS, ion mobility spectrometry (IMS)–MS and MS imaging. In particular, the integration of IMS–MS imaging and LC–IMS–MS datasets provides opportunities for spatial metabolomics analyses with increased annotation confidence.

Contains fulltext : 220554.pdf (publisher's version ) (Open Access), Platinum-based chemotherapeutics exhibit excellent antitumor properties. However, these drugs cause severe side effects including toxicity, drug resistance, and lack of tumor selectivity. Tumor-targeted drug delivery has demonstrated great potential to overcome these drawbacks. Herein, we aimed to design radioactive bisphosphonate-functionalized platinum ((195m)Pt-BP) complexes to confirm preferential accumulation of these Pt-based drugs in metabolically active bone. In vitro NMR studies revealed that release of Pt from Pt BP complexes increased with decreasing pH. Upon systemic administration to mice, Pt-BP exhibited a 4.5-fold higher affinity to bone compared to platinum complexes lacking the bone-seeking bisphosphonate moiety. These Pt-BP complexes formed less Pt-DNA adducts compared to bisphosphonate-free platinum complexes, indicating that in vivo release of Pt from Pt-BP complexes proceeded relatively slow. Subsequently, radioactive (195m)Pt-BP complexes were synthesized using (195m)Pt(NO3)2(en) as precursor and injected intravenously into mice. Specific accumulation of (195m)Pt-BP was observed at skeletal sites with high metabolic activity using micro-SPECT/CT imaging. Furthermore, laser ablation-ICP-MS imaging of proximal tibia sections confirmed that (195m)Pt BP co-localized with calcium in the trabeculae of mice tibia.

Cisplatin (CDDP) is one of the most important chemotherapeutic drugs in modern oncology. However, its use is limited by severe toxicities, which impair life quality after cancer. Here, we investigated the role of organic cation transporters (OCT) in mediating toxicities associated with chronic (twice the week for 4 weeks) low-dose (4 mg/kg body weight) CDDP treatment (resembling therapeutic protocols in patients) of wild-type (WT) mice and mice with OCT genetic deletion (OCT1/2−/−). Functional and molecular analysis showed that OCT1/2−/− mice are partially protected from CDDP-induced nephrotoxicity and peripheral neurotoxicity, whereas ototoxicity was not detectable. Surprisingly, proteomic analysis of the kidneys demonstrated that genetic deletion of OCT1/2 itself was associated with significant changes in expression of proinflammatory and profibrotic proteins which are part of an OCT-associated protein network. This signature directly regulated by OCT consisted of three classes of proteins, viz., profibrotic proteins, proinflammatory proteins, and nutrient sensing molecules. Consistent with functional protection, CDDP-induced proteome changes were more severe in WT mice than in OCT1/2−/− mice. Laser ablation-inductively coupled plasma-mass spectrometry analysis demonstrated that the presence of OCT was not associated with higher renal platinum concentrations. Taken together, these results redefine the role of OCT from passive membrane transporters to active modulators of cell signaling in the kidney.

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Diagnosis and localization of bacterial infections remains a significant clinical challenge. Harnessing bacteria-specific metabolic pathways, such as the maltodextrin transport mechanism, may allow specific localization and imaging of small or hidden colonies. This requires that the intrabacterial tracer accumulation provided by the transporter is matched by high serum stability of the tracer molecule. Herein, radiolabeled maltodextrins of varying chain lengths and with free nonreducing/reducing ends are reported and their behavior against starch-degrading enzymes in the blood, which compromise their serum stability, is evaluated. Successful single-photon emission computed tomography (SPECT) imaging is shown in a footpad infection model in vivo by using the newly developed model tracer, [99mTc]MB1143, and the signal is compared with that of 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) as a nonbacterial specific marker for inflammation. Although the [99mTc]MB1143 imaging signal is highly specific, it is low, most probably due to insufficient serum stability of the tracer. A series of stability tests with different 18F-labeled maltodextrins finally yielded clear structural guidelines regarding substitution patterns and chain lengths of maltodextrin-based tracers for nuclear imaging of bacterial infections.

© 2017 Elsevier B.V. Technetium (Tc) and Gadolinium (Gd) are the two most widely used metals in diagnostic medicine for scintigraphies and magnet resonance imaging (MRI), respectively. They play a crucial role for the generation or enhancement of contrast and are indispensable in countless diagnostic applications. However, the use of such contrast agents has caused severe health issues and environmental anomalies. This review aims to point out current issues and developments regarding the role and the analysis of these trace metals in medicine and the environment. Basic principles, issues and state of art of analytical methodologies are summarized. Current and future trends and the suggested implementation of novel methodologies and instrumentation are presented.

© 2017, Springer-Verlag GmbH Germany. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. The main functions of these metalloproteinases are the degradation of the stromal connective tissue and basement membrane components. Recent data from model systems suggest that MMPs are involved in breast cancer (BC) initiation, invasion, and metastasis. Particularly, MMP-11 (stromelysin-3) is expressed in stromal fibroblasts adjacent to epithelial tumor cells, and high levels of this metalloproteinase were associated with tumor progression and poor prognosis of BC. Consequently, MMP-11 involved in these processes can be a candidate as a new potential prognostic biomarker in BC. Bioimaging techniques based on laser ablation/desorption and mass spectrometry are rapidly growing in biology and medicine for studies of biological systems to provide information of biomolecules (such as proteins, metabolites, and lipids) and metals with lateral resolution at the micrometer scale. In this study, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has been used for the first time to investigate the distribution of MMP-11 in human breast cancer tissues in order to show a possible correlation between cancerous and healthy samples, by differential proteomics and using such differences for possible cancer diagnosis and/or prognosis. Additionally, those human breast tissue samples were analyzed in parallel by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) in order to gather additional information about the elemental distribution of Zn and its possible associations with MMPs.

© 2018 The Royal Society of Chemistry. The likelihood of exposure to antimicrobial silver nanoparticles continues to grow with their increasing ubiquity in various medical and consumer products. While translocation of silver nanoparticles to major organs has been examined, the in situ location and concentration in the organs is not well characterised. Here we have used laser ablation-inductively coupled plasma-mass spectrometry to quantitatively image serial sections to construct a three-dimensional representation of the distribution of silver in rat spleen following respiratory tract exposure via intratracheal instillation of silver nanoparticles. Silver was distributed predominantly in the white pulp of the spleen at concentrations greater than 300 ng g-1. Imaging tissue sections via laser-ablation-inductively coupled plasma-mass spectrometry is an excellent tool for the visualisation and quantification of metals attributed to nanoparticles in organs allowing investigation of silver nanoparticle exposure in vivo.

© 2017 Elsevier GmbH A novel quantification method named isobaric dilution analysis (IBDA) is introduced for internal calibration using inductively coupled plasma mass spectrometry (ICP-MS). Unlike isotope dilution analysis (IDA), where a sample to be analysed for a target analyte element is spiked with an isotopically enriched solution of the same element, IBDA uses the fact that conventional mass analysers cannot distinguish between two isobaric isotopes of different elements. Therefore, in IBDA, the sample with the element of interest is spiked with a solution of a different element, which shares at least one isobaric isotope and shows similar chemical properties resulting in a similar response. This method offers a less expensive alternative to conventional IDA especially for long-lived radionuclides of elements for which a spiking element that fulfils the above mentioned requirements can be provided. In addition, IBDA offers the advantage of making certain metastable, sometimes monoisotopic elements accessible to internal calibration using a strategy analogous to IDA. One of the elements accessible by the new calibration strategy is technetium (Tc), which suffers from a lack of standards due to safety requirements associated with its radioactivity. In this work, the principle of IBDA is first demonstrated for a certified gadolinium standard, which was diluted with a dysprosium spike exhibiting an isobaric isotope with m/z 160. The results obtained by IBDA were compared with those obtained by a conventional IDA. The concept of IBDA was subsequently used for the determination of 99Tc in a contrast agent. Since no certified Tc standards are available, the response of 99Tc was interpolated allowing accurate determinations with an uncertainty of 1%.