Increased zinc accumulation in mineralized osteosarcoma tissue measured by confocal synchrotron radiation micro X-ray fluorescence analysis

Rauwolf, Mirjam; Pemmer, Bernhard; Roschger, Andreas; Turyanskaya, Anna; Smolek, S.; Maderitsch, A.; Hischenhuber, Peter; Foelser, Martin; Simon, R.; Lang, Susanna; Puchner, Stefan; Windhager, Reinhard; Klaushofer, Klaus; Wobrauschek, P.; Hofstaetter, Jochen G.; Roschger, Paul; Streli, Christina

doi:10.1002/xrs.2727

Cited by 15 publications

(8 citation statements)

References 43 publications

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“…Recent SR XRF studies also targeted osteosarcoma-the most common bone cancer in children and teens in which tumor cells produce immature bone also known as osteoid (the un-mineralized organic part of the bone matrix during bone formation). As reported by Rauwolf et al [85] and Streli et al [86], the Zn levels in the bone regions affected by osteosarcoma were found to be significantly higher than those in the healthy regions within the same bone sample. On average, the Zn fraction median in osteosarcoma regions, defined as the median of the relative counts ratio Zn/(Zn + Ca) distribution, was found to be about six times higher than that measured in healthy bone regions.…”

Section: Bone Teeth and Internal Organssupporting

confidence: 66%

“…More detailed synchrotron-based XRF data and more in-depth relationships with bone and joint anatomy, physiology, and histopathology were revealed and discussed in several papers published by an extended European research collaboration over the past 15 years [82][83][84][85][86]. A common denominator of these bone studies is the comparison of the synchrotron-based XRF elemental imaging and analysis with the images obtained from quantitative backscattered electron imaging (qBEI)-a scanning electron microscope (SEM) technique developed in the 1990s [87] which measured Ca concentration at a few micrometers spatial resolution based on a calibration with grey scale values from SEM images.…”

Section: Bone Teeth and Internal Organsmentioning

confidence: 99%

“…Since Zn is known to be a stimulant of bone mineralization, the observed high Zn concentration level in poorly mineralized tumorous tissue seems counterintuitive. In the larger cancer research context, Rauwolf et al [85] listed studies which reported decreased Zn levels in several types of cancer (a notable exception was the breast cancer study of Al-Ebraheem et al [67]). As possible speculative explanations for the elevated Zn levels in osteosarcoma tissues, the authors pointed to: i) the possible effects of chemotherapy on Zn levels and ii) the reported low levels of Zn in serum bone turnover markers such as bone alkaline phosphatase in children and adolescents with osteosarcoma-an observation that would support the Zn accumulation in the bone tissue malignancies by depletion of Zn in the serum.…”

Section: Bone Teeth and Internal Organsmentioning

confidence: 99%

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Probing Trace Elements in Human Tissues with Synchrotron Radiation

Gherase

Fleming

2019

Crystals

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For the past several decades, synchrotron radiation has been extensively used to measure the spatial distribution and chemical affinity of elements found in trace concentrations (<few µg/g) in animal and human tissues. Intense and highly focused (lateral size of several micrometers) X-ray beams combined with small steps of photon energy tuning (2–3 eV) of synchrotron radiation allowed X-ray fluorescence (XRF) and X-ray absorption spectroscopy (XAS) techniques to nondestructively and simultaneously detect trace elements as well as identify their chemical affinity and speciation in situ, respectively. Although limited by measurement time and radiation damage to the tissue, these techniques are commonly used to obtain two-dimensional and three-dimensional maps of several elements at synchrotron facilities around the world. The spatial distribution and chemistry of the trace elements obtained is then correlated to the targeted anatomical structures and to the biological functions (normal or pathological). For example, synchrotron-based in vitro studies of various human tissues showed significant differences between the normal and pathological distributions of metallic trace elements such as iron, zinc, copper, and lead in relation to human diseases ranging from Parkinson’s disease and cancer to osteoporosis and osteoarthritis. Current research effort is aimed at not only measuring the abnormal elemental distributions associated with various diseases, but also indicate or discover possible biological mechanisms that could explain such observations. While a number of studies confirmed and strengthened previous knowledge, others revealed or suggested new possible roles of trace elements or provided a more accurate spatial distribution in relation to the underlying histology. This area of research is at the intersection of several current fundamental and applied scientific inquiries such as metabolomics, medicine, biochemistry, toxicology, food science, health physics, and environmental and public health.

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Section: Bone Teeth and Internal Organssupporting

confidence: 66%

Section: Bone Teeth and Internal Organsmentioning

confidence: 99%

Section: Bone Teeth and Internal Organsmentioning

confidence: 99%

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Probing Trace Elements in Human Tissues with Synchrotron Radiation

Gherase

Fleming

2019

Crystals

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“…However, very little is known about the distribution of Gd in bone on the microscopic level. Our group has already employed the method of synchrotron radiation induced micro-X-ray fluorescence (SR-micro-XRF) for the characterization of distribution of trace elements, such as lead (Pb), zinc (Zn) and strontium (Sr) in healthy and diseased bone and cartilage samples [20][21][22] . Within this project we applied SR-micro-and submicro-XRF for the detection and mapping of Gd distribution within bone tissue.…”

mentioning

confidence: 99%

Detection and imaging of gadolinium accumulation in human bone tissue by micro- and submicro-XRF

Turyanskaya

Rauwolf

Pichler

et al. 2020

Sci Rep

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Gadolinium-based contrast agents (GBcAs) are frequently used in patients undergoing magnetic resonance imaging. in GBcAs gadolinium (Gd) is present in a bound chelated form. Gadolinium is a rareearth element, which is normally not present in human body. though the blood elimination half-life of contrast agents is about 90 minutes, recent studies demonstrated that some tissues retain gadolinium, which might further pose a health threat due to toxic effects of free gadolinium. It is known that the bone tissue can serve as a gadolinium depot, but so far only bulk measurements were performed. Here we present a summary of experiments in which for the first time we mapped gadolinium in bone biopsy from a male patient with idiopathic osteoporosis (without indication of renal impairment), who received MRI 8 months prior to biopsy. In our studies performed by means of synchrotron radiation induced micro-and submicro-X-ray fluorescence spectroscopy (SR-XRF), gadolinium was detected in human cortical bone tissue. The distribution of gadolinium displays a specific accumulation pattern. Correlation of elemental maps obtained at AnKA synchrotron with qBei images (quantitative backscattered electron imaging) allowed assignment of Gd structures to the histological bone structures. follow-up beamtimes at eSRf and Diamond Light Source using submicro-SR-XRf allowed resolving thin Gd structures in cortical bone, as well as correlating them with calcium and zinc. The method of contrast-enhanced MRI (CE-MRI) dates to 1988, when the first gadolinium (Gd)-based contrast agent (GBCA), gadopentetate dimeglumine (Magnevist, Bayer), was approved for clinical use. CE-MRI is a useful imaging tool nowadays, with approximately 30 million procedures done each year worldwide, and more than 300 million procedures already performed to date 1. Estimates show that the GBCAs are administered in 25-35% of all MRI examinations 1,2. According to the data available, most of the administered dose of GBCAs (regardless of an agent used), should be cleared in less than 2 and >95% by 24 hours 3. Recent findings, however, demonstrate that the GBCAs are not fully excreted and the accumulation of Gd in, e.g. neuronal tissues and organs such as brain takes place 4. The GBCAs are considered to be rather safe, yet there is a number of papers reporting nephrotoxic, hematotoxic, hepatotoxic and neurotoxic effects observed in animals and humans 5. One of the most serious adverse reactions associated with the use of GBCAs is nephrogenic systemic fibrosis (NSF), which had been observed in patients with renal insufficiency 6. NSF is a rare, but serious disease characterized by widespread tissue hardening (primarily skin is affected) with fibrotic nodules and plaques. First described in 1997, it was finally linked to the use of GBCAs in patients with kidney dysfunction in 2006 6,7. The pathophysiological mechanism involved

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“…Such research has provided insights into biogenic “baselines” and metabolic patterns of TE accumulation in bone and dental tissues (Kang et al 2004 ; Zoeger et al 2005 , 2008 ; de Souza-Guerra et al 2010 , 2014 ; Pemmer et al 2013 ; Wang et al 2017 ). Use of SR-XFI to map the disproportionate distribution of TEs such as Pb and Zn in modern bone with respect to diseases such as osteoarthritis and osteosarcomas (Zoeger et al 2008 ; Rauwolf et al 2017 ) may also aid in palaeopathological interpretations, potentially including cases where the diseases were still in early stages at death. Overall, research in this area has produced several valuable takeaways for the bioarchaeological interpretation of TE variation within specific developmental junctures.…”

Section: Resurgence Of Trace Element Analysis? Techniques With Growinmentioning

confidence: 99%

Historical overview and new directions in bioarchaeological trace element analysis: a review

Simpson

Cooper

Swanston

et al. 2021

Archaeol Anthropol Sci

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Given their strong affinity for the skeleton, trace elements are often stored in bones and teeth long term. Diet, geography, health, disease, social status, activity, and occupation are some factors which may cause differential exposure to, and uptake of, trace elements, theoretically introducing variability in their concentrations and/or ratios in the skeleton. Trace element analysis of bioarchaeological remains has the potential, therefore, to provide rich insights into past human lifeways. This review provides a historical overview of bioarchaeological trace element analysis and comments on the current state of the discipline by highlighting approaches with growing momentum. Popularity for the discipline surged following preliminary studies in the 1960s to 1970s that demonstrated the utility of strontium (Sr) as a dietary indicator. During the 1980s, Sr/Ca ratio and multi-element studies were commonplace in bioarchaeology, linking trace elements with dietary phenomena. Interest in using trace elements for bioarchaeological inferences waned following a period of critiques in the late 1980s to 1990s that argued the discipline failed to account for diagenesis, simplified complex element uptake and regulation processes, and used several unsuitable elements for palaeodietary reconstruction (e.g. those under homeostatic regulation, those without a strong affinity for the skeleton). In the twenty-first century, trace element analyses have been primarily restricted to Sr and lead (Pb) isotope analysis and the study of toxic trace elements, though small pockets of bioarchaeology have continued to analyse multiple elements. Techniques such as micro-sampling, element mapping, and non-traditional stable isotope analysis have provided novel insights which hold the promise of helping to overcome limitations faced by the discipline.

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Increased zinc accumulation in mineralized osteosarcoma tissue measured by confocal synchrotron radiation micro X-ray fluorescence analysis

Cited by 15 publications

References 43 publications

Probing Trace Elements in Human Tissues with Synchrotron Radiation

Probing Trace Elements in Human Tissues with Synchrotron Radiation

Detection and imaging of gadolinium accumulation in human bone tissue by micro- and submicro-XRF

Historical overview and new directions in bioarchaeological trace element analysis: a review

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