X-ray fluorescence imaging could open up new diagnostic possibilities in medicine

Using gold to track down diseases

A high-precision X-ray technique, tested at PETRA III, could catch cancer at an earlier stage and facilitate the development and control of pharmaceutical drugs. The test at DESY’s synchrotron radiation source, which used so-called X-ray fluorescence for that purpose, has proved very promising, as is now being reported in the journal Scientific Reports by a research team headed by Florian Grüner from the University of Hamburg. The technique is said to offer the prospect of carrying out such X-ray studies not only with higher precision than existing methods but also with less of a dose impact. However, before the method can be used in a clinical setting, it still has to undergo numerous stages of development.

The idea behind the procedure is simple: tiny nanoparticles of gold having a diameter of twelve nanometres (millionths of a millimetre) are functionalised with antibodies using biochemical methods. “A solution containing such nanoparticles is injected into the patient,” explains Grüner, a professor of physics at the Centre for Free-Electron Laser Science (CFEL), a cooperative venture between DESY, the University of Hamburg and the Max Planck Society. “The particles migrate through the body, where the antibodies can latch onto a tumour that may be present.” When the corresponding parts of the patient’s body are scanned using a pencil X-ray beam, the gold particles emit characteristic X-ray fluorescence signals, which are recorded by a special detector. The hope is that this will permit the detection of tiny tumours that cannot be found using current methods.

>Read more on the PETRA III at DESY website

Image: Gold nanoparticles spiked with antibodies can specifically attach to tumors or other targets in the organism and can be detected there by X-ray fluorescence.
Credit: Meletios Verras [Source]

SESAME hosts its first users

Mid July, the first users arrived at SESAME to perform experiments using the Centre’s XAFS/XRF (X-ray absorption fine structure/X-ray fluorescence) spectroscopy beamline, SESAME’s first beamline to come into operation.

This was the Finnish Kirsi Lorentz and three of her colleagues at The Cyprus Institute: the Cypriot Grigoria Ioannou, the Japanese Yuko Miyauchi and the Greek/Egyptian Iosif Hafez, who together form a true international team in the spirit of SESAME.

Kirsi is the author of one of the 19 proposals from 5 of the SESAME Members (Cyprus, Egypt, Jordan, Pakistan and Turkey) that have been recommended for a total of 95.8 hour shifts on the XAFS/XRF beamline by SESAME’s Proposal Review Committee (PRC). The PRC is an international advisory body that evaluates the scientific and technological merit of proposals from the General Users and determines their priority using criteria based on IUPAP’s Recommendations for the Use of Major Physics Users Facilities.

“This heralds in a new stage in SESAME’s march forward, and for scientists in the SESAME Members and the region it is the tangible beginning of a moment from when it becomes possible to carry out state-of-the-art research in the region” said Khaled Toukan, Director of SESAME.

 “It is a unique opportunity and a real honour to be the first user of a synchrotron light facility – a research visit to remember” said Kirsi, who is examining ancient human remains from the Eastern Mediterranean and the Near East, adding “we are very excited with the results we obtained at the SESAME XAFS/XRF beamline, and grateful to all those who have worked so hard to bring this crucial research facility into operation in our region”.

>Read more on the SESAME website

Picture: Kirsi Lorentz, The Cyprus Institute: Kirsi Lorentz and her research team (from left to right: Yuko Miyauchi, Grigoria Ioannou, Kirsi Lorentz and Iosif Hafez) at the XAFS/XRF beamline control hutch.

Enlightening yellow in art

Scientists from the University of Perugia (Italy), CNR (Italy), University of Antwerp, the ESRF and DESY, have discovered how masterpieces degrade over time in a new study with mock-up paints carried out at synchrotrons ESRF and DESY. Humidity, coupled with light, appear to be the culprits.

The Scream by Munch, Flowers in a blue vase by Van Gogh or Joy of Life by Matisse, all have something in common: their cadmium yellow pigment. Throughout the years, this colour has faded into a whitish tone and, in some instances, crusts of the paint have arisen, as well as changes in the morphological properties of the paint, such as flaking or crumbling. Conservators and researchers have come to the rescue though, and they are currently using synchrotron techniques to study in depth these sulphide pigments and to find a solution to preserve them in the long run.

“This research has allowed us to make some progress. However, it is very difficult for us to pinpoint to what causes the yellow to go white as we don’t have all the information about how or where the paintings have been kept since they were done in the 19th century”, explains Letizia Monico, scientist from the University of Perugia and the CNR-ISTM. Indeed, limited knowledge of the environmental conditions (e.g., humidity, light, temperature…) in which paintings were stored or displayed over extended periods of time and the heterogeneous chemical composition of paint layers (often rendered more complex by later restoration interventions) hamper a thorough understanding of the overall degradation process.

>Read more on the ESRF website

Image: Some of the mock-up paints, prepared by Letizia Monico. Credits: C. Argoud.

Probing tumour interiors

X-ray fluorescence mapping to measure tumour penetration by a novel anticancer agent.

A new anticancer agent developed by the University of Warwick has been studied using microfocus synchrotron X-ray fluorescence (SXRF) at I18 at Diamond Light Source. As described in The Journal of Inorganic Biochemistry, researchers saw that the drug penetrated ovarian cancer cell spheroids and the distribution of zinc and calcium was perturbed.  

Platinum-based chemotherapy agents are used to treat many cancer patients, but some can develop resistance to them. To address this issue, scientists from the University of Warwick sought to employ alternative precious metals. They developed an osmium-based agent, known as FY26, which exhibits high potency against a range of cancer cell lines. To unlock the potential of this novel agent and to test its efficacy and safety in clinical trials, the team need to fully understand its mechanism of action.

To explore how FY26 behaves in tumours, the team grew ovarian cancer spheroids and used SXRF at I18 to probe the depth of penetration of the drug. They noted that FY26 could enter the cores of the spheroids, which is critical for its activity and very encouraging for the future of the drug. SXRF also enabled them to probe other metals within the cells, which showed that the distribution of zinc and calcium was altered, providing new insights into the mechanism of FY26-induced cell death.

>Read more on the Diamond Light Source website

Figure: (extract) A) Structure of FY26and related complexes, [(ŋ6-p-cym)Os(Azpy-NMe2)X]+. B) Bright field images and SXRF elemental maps of Os, Ca and Zn in A2780 human ovarian carcinoma spheroid sections (500 nm thick) treated with 0.7 µM FY26(½ IC50) for 0 or 48 h. Raster scan: 2×2 µm2 step size, 1 s dwell time. Scale bar 100 µm. Calibration bar in ng mm-2. Yellow squares in bright field images indicate areas of the spheroid studied using SXRF. Red areas in SXRF elemental maps indicate the limits of the spheroids. C) Average Os content (in ng mm-2) as a function of distance from A2780 3D spheroid surface, after treatment for 16 h (green), 24 h (blue) or 48 h (red) with 0.7 µM FY26. 

Fighting malaria with X-rays

Today 25 April, is World Malaria Day.

Considered as one of humanity’s oldest life-threatening diseases, nearly half the world population is at risk, with 216 million people affected in 91 countries worldwide in 2016. Malaria causes 445 000 deaths every year, mainly among children. The ESRF has been involved in research into Malaria since 2005, with different techniques being used in the quest to find ways to prevent or cure the disease.

Malaria in humans is caused by Plasmodium parasites, the greatest threat coming from two species: P. falciparum and P. vivax. The parasites are introduced through the bites of infected female Anopheles mosquitoes. They travel to the liver where they multiply, producing thousands of new parasites. These enter the blood stream and invade red blood cells, where they feed on hemoglobin (Hgb) in order to grow and multiply. After creating up to 20 new parasites, the red blood cells burst, releasing daughter parasites ready for new invasions. This life cycle leads to an exponential growth of infected red blood cells that may cause the death of the human host.

The research carried out over the years at the ESRF has aimed to identify mechanisms critical for the parasite’s survival in the hope of providing an intelligent basis for the development of drugs to stop the parasite’s multiplication and spread.

>Read more on the European Synchrotron website

Image: Inside the experimental hutch of the ESRF’s ID16A nano-analysis beamlin.
Credit: Pierre Jayet

Combining X-ray techniques for powerful insights into hyperaccumulator plants

The complementary power of combining multiple X-ray techniques to understand the unusual properties of hyperaccumulator plants has been highlighted in a new cover article just published in New Phytologist.

X-ray fluorescence microscopy (XFM) at the Australian Synchrotron has been used by a consortium of international researchers led by Dr Antony van der Ent of the Centre for Mined Land Rehabilitation at The University of Queensland, in association with A/Prof Peter Kopittke of the School of Agriculture and Food Science also at The University of Queensland.

The XFM technique generates elemental maps showing where elements of interest are found within plant tissue, seedlings or individual cells.
Visually striking images (obtained at the XFM beamline) show various hyperaccumulator plants, on the cover of the April issue of New Phytologist. In the images each element is depicted in a different colour, making up a red-green-blue (RGB) image.

“Hyperaccumulator plants have the unusual ability to accumulate extreme concentrations of metals and metalloids in their living tissues,” said van der Ent.
“Hyperaccumulators are of scientific interest because whilst metals are normally toxic to plants even at low concentrations, these plants are able to accumulate large concentrations without any toxic effects,” he added

>Read more on the Autralian Synchrotron website

Image: X‐ray Fluorescence (XRF) elemental maps of hyperaccumulator plants. The tricolour composite images show (left to right) root cross‐section of Senecio coronatus (red, iron; green, nickel; blue, potassium); and seedlings of Alyssum murale (red, calcium; green, nickel; blue, Compton scatter).
Credit: A. van der Ent. 

Hidden medical text read for the first time in a thousand years

With X-ray imaging at SLAC’s synchrotron, scientists uncovered a 6th century translation of a book by the Greek-Roman doctor Galen.

An influential physician and a philosopher of early Western medicine, Galen of Pergamon was the doctor of emperors and gladiators. One of his many works, “On the Mixtures and Powers of Simple Drugs,” was an important pharmaceutical text that would help educate fellow Greek-Roman doctors.

The text was translated during the 6th century into Syriac, a language that served as a bridge between Greek and Arabic and helped spread Galen’s ideas into the ancient Islamic world. But despite the physician’s fame, the most complete surviving version of the translated manuscript was erased and written over with hymns in the 11th century – a common practice at the time. These written-over documents are known as palimpsests.

An international team of researchers is getting a clear look at the hidden text of the Syriac Galen Palimpsest with an X-ray study at the Stanford Synchrotron Radiation Lightsource (SSRL) at the Department of Energy’s SLAC National Accelerator Laboratory.

>Read more on the Stanford Synchrotron Radiation Lightsource website

Image: Conservators at Stanford University Libraries removed the pages from the leather-bound cover of the book of hymns, and mounted each leaf in an individually fitted, archival mat. The individual mats were placed in an aluminum frame to secure the pages while examining the underlying text with X-rays at the Stanford Synchrotron Radiation Lightsource.
Credit:
Farrin Abbott / SLAC National Accelerator Laboratory

Technique provides insights into historic maritime artefact

Recently an advanced X-ray imaging technique was used on a historic pewter plate linked to the early exploration of Australia by the Dutch in the 17th century. X-ray fluorescence (XRF) has proven to be a highly useful analytical tool for the study of cultural objects, such as works of art and artefacts.

“The non-destructive analysis can provide information about how the objects were made, their composition and insight for conservation strategies,” said XRF beamline scientist Dr Daryl Howard.
“The fast detector on the instrument and its high sensitivity allows us to keep the exposure to radiation to a minimum, which is important for rare and valuable objects. “

In December last year, a small group from the Rijksmuseum in Amsterdam and the Queen Victoria Museum and Art Gallery (QVMAG) in Tasmania brought the Hartog Plate to the Synchrotron for scanning.

>Read more on the Australian Synchrotron website

Image: (extract) X-ray fluorescence scan image showing elemental distribution of bismuth (red) lead (green) and germanium (blue). Entire picture here.