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Molecular Research of Biomedical X-ray Fluorescence Imaging (XFI)
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Molecular Research of Biomedical X-ray Fluorescence Imaging (XFI)

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 February 2025) | Viewed by 10033

Special Issue Editor

Prof. Dr. Florian Grüner

E-Mail Website
Guest Editor
Institut für Experimentalphysik, University of Hamburg | UHH, Hamburg, Germany
Interests: plasma accelerators; free electron lasers; X-ray laser; x-ray fluorescence imaging

Special Issue Information

Dear Colleagues,

The use of X-rays for studies in biology, material science, and medicine has been established over many decades and led to new insights into probes without the need for cutting them open.

A novel molecular imaging modality for biomedical and plant science applications is X-ray fluorescence imaging (XFI) which uses a scanning X-ray pencil beam to excite characteristic X-ray fluorescence photons. XFI is, thus, a spectroscopic X-ray method and offers both a high sensitivity and a high spatial resolution at the same time. Different to optical methods, XFI does not face depth limitations and since the used markers, typically either metallic nanoparticles or molecular tracers such as iodine, do not decay over time, measurements can be done over arbitrarily long time windows. Being a truly multi-scale modality, XFI-measurements can already be conducted from the single-cell level or small plant samples up to full-body in-vivo scans in preclinical setups. In addition, XFI allows for multiplexing or multi-tracking, respectively, i.e. the simultaneous tracking of different labels in the same probe. Key applications could be pharmacokinetics, i.e. the tracking of medical drug molecules like cytostatics in oncology, or even cell tracking, where the cells, e.g. immune or killer cells, are labeled with molecular tracers.

A further application in biomedical studies could be the measuring of the uptake of labeled molecules into cells, e.g. chemotherapeutics into tumor cells, a key step in molecular drug development. XFI can also be used in material science, e.g. for non-destructive testing or analyses of specific elements in small samples.

Over the last years, the field of XFI has brought up many promising breakthroughs helping biomedical and material research. With this Special Issue we want to make this promising imaging modality even more visible, in particular for interdisciplinary researchers.

We encourage the submission of original full research papers as well as review articles dealing with new developments in the field of XFI, both for biomedical as well as material research. Articles reporting new applications of XFI or novel strategies on further developments of the XFI-technique, as well as manuscripts that focus on translating this modality to new medical applications in clinics are highly welcomed.

Prof. Dr. Florian Grüner
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • X-ray fluorescence imaging
  • biomedical imaging
  • pharmacokinetics
  • drug development
  • non-desctructing testing

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Published Papers (5 papers)

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Research

13 pages, 2707 KiB  
Article
Iodinated PSMA Ligands as XFI Tracers for Targeted Cell Imaging and Characterization of Nanoparticles
by Svenja Kerpa, Malte Holzapfel, Theresa Staufer, Robert Kuhrwahl, Marina Mutas, Stefan Werner, Verena R. Schulze, Pascal Nakielski, Neus Feliu, Elke Oetjen, Jannis Haak, Florian Ziegler, Rasmus Buchin, Jili Han, Wolfgang J. Parak, Florian Grüner and Wolfgang Maison
Int. J. Mol. Sci. 2024, 25(22), 11880; https://doi.org/10.3390/ijms252211880 - 5 Nov 2024
Viewed by 1169
Abstract
Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Despite this, current diagnostic tools are still not satisfactory, lacking sensitivity for early-stage or single-cell diagnosis. This study describes the development of small-molecule tracers for the well-known tumor marker prostate-specific membrane [...] Read more.
Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Despite this, current diagnostic tools are still not satisfactory, lacking sensitivity for early-stage or single-cell diagnosis. This study describes the development of small-molecule tracers for the well-known tumor marker prostate-specific membrane antigen (PSMA). These tracers contain a urea motif for PSMA-targeting and iodinated aromatic moieties to allow detection via X-ray fluorescence imaging (XFI). Tracers with a triiodobenzoyl moiety allowed the specific targeting and successful imaging of PSMA+ cell lines with XFI. The XFI-measured uptake of 7.88 × 10−18 mol iodine (I) per cell is consistent with the uptake of known PSMA tracers measured by other techniques such as inductively coupled plasma mass spectrometry (ICP-MS). This is the first successful application of XFI to tumor cell targeting with a small-molecule tracer. In addition, iodinated tracers were used for the characterization of quantum dots (QDs) conjugated to PSMA-targeting urea motifs. The resulting targeted QD conjugates were shown to selectively bind PSMA+ cell lines via confocal microscopy. The immobilized iodinated targeting vectors allowed the determination of the tracer/QD ratio via XFI and ICP-MS. This ratio is a key property of targeted particles and difficult to measure by other techniques. Full article
(This article belongs to the Special Issue Molecular Research of Biomedical X-ray Fluorescence Imaging (XFI))
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18 pages, 12466 KiB  
Article
X-ray Fluorescence Microscopy to Develop Elemental Classifiers and Investigate Elemental Signatures in BALB/c Mouse Intestine a Week after Exposure to 8 Gy of Gamma Rays
by Anthony Smith, Katrina Dobinda, Si Chen, Peter Zieba, Tatjana Paunesku, Zequn Sun and Gayle E. Woloschak
Int. J. Mol. Sci. 2024, 25(19), 10256; https://doi.org/10.3390/ijms251910256 - 24 Sep 2024
Viewed by 892
Abstract
Iron redistribution in the intestine after total body irradiation is an established phenomenon. However, in the literature, there are no reports about the use of X-ray fluorescence microscopy or equivalent techniques to generate semi-quantitative 2D maps of iron in sectioned intestine samples from [...] Read more.
Iron redistribution in the intestine after total body irradiation is an established phenomenon. However, in the literature, there are no reports about the use of X-ray fluorescence microscopy or equivalent techniques to generate semi-quantitative 2D maps of iron in sectioned intestine samples from irradiated mice. In this work, we used X-ray fluorescence microscopy (XFM) to map the elemental content of iron as well as phosphorus, sulfur, calcium, copper and zinc in tissue sections of the small intestine from eight-week-old BALB/c male mice that developed gastrointestinal acute radiation syndrome (GI-ARS) in response to exposure to 8 Gray of gamma rays. Seven days after irradiation, we found that the majority of the iron is localized as hot spots in the intercellular regions of the area surrounding crypts and stretching between the outer perimeter of the intestine and the surface cell layer of villi. In addition, this study represents our current efforts to develop elemental cell classifiers that could be used for the automated generation of regions of interest for analyses of X-ray fluorescence maps. Once developed, such a tool will be instrumental for studies of effects of radiation and other toxicants on the elemental content in cells and tissues. While XFM studies cannot be conducted on living organisms, it is possible to envision future scenarios where XFM imaging of single cells sloughed from the human (or rodent) intestine could be used to follow up on the progression of GI-ARS. Full article
(This article belongs to the Special Issue Molecular Research of Biomedical X-ray Fluorescence Imaging (XFI))
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26 pages, 7956 KiB  
Article
High-Spatial-Resolution Benchtop X-ray Fluorescence Imaging through Bragg-Diffraction-Based Focusing with Bent Mosaic Graphite Crystals: A Simulation Study
by Kunal Kumar, Melanie Fachet and Christoph Hoeschen
Int. J. Mol. Sci. 2024, 25(9), 4733; https://doi.org/10.3390/ijms25094733 - 26 Apr 2024
Cited by 2 | Viewed by 2358
Abstract
X-ray fluorescence imaging (XFI) can localize diagnostic or theranostic entities utilizing nanoparticle (NP)-based probes at high resolution in vivo, in vitro, and ex vivo. However, small-animal benchtop XFI systems demonstrating high spatial resolution (variable from sub-millimeter to millimeter range) in vivo are still [...] Read more.
X-ray fluorescence imaging (XFI) can localize diagnostic or theranostic entities utilizing nanoparticle (NP)-based probes at high resolution in vivo, in vitro, and ex vivo. However, small-animal benchtop XFI systems demonstrating high spatial resolution (variable from sub-millimeter to millimeter range) in vivo are still limited to lighter elements (i.e., atomic number Z≤45). This study investigates the feasibility of focusing hard X-rays from solid-target tubes using ellipsoidal lens systems composed of mosaic graphite crystals with the aim of enabling high-resolution in vivo XFI applications with mid-Z (42≤Z≤64) elements. Monte Carlo simulations are performed to characterize the proposed focusing-optics concept and provide quantitative predictions of the XFI sensitivity, in silico tumor-bearing mice models loaded with palladium (Pd) and barium (Ba) NPs. Based on simulation results, the minimum detectable total mass of PdNPs per scan position is expected to be on the order of a few hundred nanograms under in vivo conform conditions. PdNP masses as low as 150 ng to 50 ng could be detectable with a resolution of 600 μm when imaging abdominal tumor lesions across a range of low-dose (0.8 μGy) to high-dose (8 μGy) exposure scenarios. The proposed focusing-optics concept presents a potential step toward realizing XFI with conventional X-ray tubes for high-resolution applications involving interesting NP formulations. Full article
(This article belongs to the Special Issue Molecular Research of Biomedical X-ray Fluorescence Imaging (XFI))
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11 pages, 2627 KiB  
Article
Laboratory Liquid-Jet X-ray Microscopy and X-ray Fluorescence Imaging for Biomedical Applications
by Komang G. Y. Arsana, Giovanni M. Saladino, Bertha Brodin, Muhammet S. Toprak and Hans M. Hertz
Int. J. Mol. Sci. 2024, 25(2), 920; https://doi.org/10.3390/ijms25020920 - 11 Jan 2024
Cited by 3 | Viewed by 2710
Abstract
Diffraction-limited resolution and low penetration depth are fundamental constraints in optical microscopy and in vivo imaging. Recently, liquid-jet X-ray technology has enabled the generation of X-rays with high-power intensities in laboratory settings. By allowing the observation of cellular processes in their natural state, [...] Read more.
Diffraction-limited resolution and low penetration depth are fundamental constraints in optical microscopy and in vivo imaging. Recently, liquid-jet X-ray technology has enabled the generation of X-rays with high-power intensities in laboratory settings. By allowing the observation of cellular processes in their natural state, liquid-jet soft X-ray microscopy (SXM) can provide morphological information on living cells without staining. Furthermore, X-ray fluorescence imaging (XFI) permits the tracking of contrast agents in vivo with high elemental specificity, going beyond attenuation contrast. In this study, we established a methodology to investigate nanoparticle (NP) interactions in vitro and in vivo, solely based on X-ray imaging. We employed soft (0.5 keV) and hard (24 keV) X-rays for cellular studies and preclinical evaluations, respectively. Our results demonstrated the possibility of localizing NPs in the intracellular environment via SXM and evaluating their biodistribution with in vivo multiplexed XFI. We envisage that laboratory liquid-jet X-ray technology will significantly contribute to advancing our understanding of biological systems in the field of nanomedical research. Full article
(This article belongs to the Special Issue Molecular Research of Biomedical X-ray Fluorescence Imaging (XFI))
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16 pages, 3704 KiB  
Article
Probing the Cellular Fate of the Protein Corona around Nanoparticles with Nanofocused X-ray Fluorescence Imaging
by Marvin Skiba, Gabriela Guedes, Dmitry Karpov, Neus Feliu, Aitziber L. Cortajarena, Wolfgang J. Parak and Carlos Sanchez-Cano
Int. J. Mol. Sci. 2024, 25(1), 528; https://doi.org/10.3390/ijms25010528 - 30 Dec 2023
Cited by 3 | Viewed by 2034
Abstract
X-ray fluorescence imaging (XRF-imaging) with subcellular resolution is used to study the intracellular integrity of a protein corona that was pre-formed around gold nanoparticles (AuNP). Artificial proteins engineered to obtain Gd coordination for detection by XRF-imaging were used to form the corona. Indications [...] Read more.
X-ray fluorescence imaging (XRF-imaging) with subcellular resolution is used to study the intracellular integrity of a protein corona that was pre-formed around gold nanoparticles (AuNP). Artificial proteins engineered to obtain Gd coordination for detection by XRF-imaging were used to form the corona. Indications about the degradation of this protein corona at a cellular and subcellular level can be observed by following the Au and Gd quantities in a time and spatial-dependent manner. The extended acquisition times necessary for capturing individual XRF-imaging cell images result in relatively small sample populations, stressing the need for faster image acquisition strategies in future XRF-imaging-based studies to deal with the inherent variability between cells. Still, results obtained reveal degradation of the protein corona during cellular trafficking, followed by differential cellular processing for AuNP and Gd-labelled proteins. Overall, this demonstrates that the dynamic degradation of the protein corona can be tracked by XRF-imaging to a certain degree. Full article
(This article belongs to the Special Issue Molecular Research of Biomedical X-ray Fluorescence Imaging (XFI))
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