PRESS RELEASE
January 29, 2021
On the Dot: Novel Quantum Sensor Provides New Approach
to Early Diagnosis Via Imaging
Chiba, Japan - Scientists develop new quantum sensor that allows detection of “oxidativestress” in organs during MRI scans, opening doors to early diagnosis of serious illnesses
A phenomenon called “oxidative stress” is seen in affected organs during the early stagesof certain difficult-to-treat diseases like cancer and kidney dysfunction. Detecting
oxidative stress could thus enable early diagnosis and preventive treatments. But, the invivo measurement of oxidative stress caused by both oxidation and reduction has
historically been difficult. Now, scientists have developed an advanced quantum sensor
technology that can detect “oxidative stress” non-invasively throughout the body using
fluorescent imaging and MRI.
Oxygen is essential for human life, but within the body, certain biological environmental
conditions can transform oxygen into aggressively reactive molecules called reactive oxygenspecies (ROS), which can damage DNA, RNA, and proteins. Normally, the body relies onmolecules called antioxidants to convert ROS into less dangerous chemical species through aprocess called reduction. But unhealthy lifestyles, various diseases, stress, and aging can allcontribute to an imbalance between the production of ROS and the body’s ability to reduce andeliminate them. The resulting excessive levels of ROS cause “oxidative stress,” which candisrupt normal cellular functions and increase the risk of diseases like cancer,
neurodegeneration, kidney dysfunction, and others, which are all accompanied by severe
inflammation.
Since oxidative stress is associated with various serious diseases, its detection within livingorgans offers a route to early diagnosis and preventive treatment, and is, thus, a matter ofconsiderable interest to scientists working in the field of biomedicine. Recent international
collaboration between the Japanese National Institutes for Quantum and Radiological Scienceand Technology (QST), Bulgarian Academy of Sciences, and Sofia University St. Kliment
Ohridski in Bulgaria led to a promising technology for this purpose: a novel quantum sensor.
Their work is published in the scientific journal Analytical Chemistry, 2021.

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According to lead scientist Dr. Rumiana Bakalova and her colleague Dr. Ichio Aoki of QST,
“the new sensor is appropriate for the early diagnosis of pathologies accompanied byinflammation, such as infectious diseases, cancer, neurodegeneration, atherosclerosis,diabetes, and kidney dysfunction.”
The sensor comprises a quantum dot—semiconductor—core coated with a ring-shaped sugarlike compound called α-cyclodextrin, which in turn is bonded to six redox-sensitive chemicalgroups called nitroxide derivatives. These components have the advantage of favorable safety
profiles, with cyclodextrins being approved for use in food and nitroxide derivatives being
considered generally harmless for living beings due to their antioxidant properties.
The nitroxide derivatives cause the sensor to give ON fluorescence signals when in a reduced
state and give ON magnetic signals when in an oxidized state. This allows for the detection ofoxidative stress, or a reduced cell/tissue capacity, using methods such as magnetic resonanceimaging (MRI) and electron paramagnetic imaging (EPR), which can detect magnetic signals.
The chemical sensor is also bonded to a compound called triphenylphosphonium, which helps
the sensor enter living cells and proceed to the mitochondria, which are the cellular components
most often responsible for generating ROS, particularly under pathologic conditions.
To test their novel chemical sensor, the scientists first performed experiments with cultures ofnormal (healthy) and cancerous colon cells in the lab. For this they used their sensor in theoxidized form. In healthy cells, EPR signals were quenched; but in cancer cells, they stayedstrong. This indicates that the sensors were reduced in healthy cells by antioxidants butremained in their oxidized state in the cancer cells, which in turn suggests that the cancerous
cells had a higher oxidative capacity.
To further test the sensor, the researchers conducted experiments with both healthy mice andthose that had been raised on a high-cholesterol diet for 2 months, which caused them todevelop early-stage kidney dysfunction due to persistent inflammation. Compared with thehealthy mice, the mice with kidney dysfunction exhibited stronger MRI signals in their kidneys,
suggesting that their kidneys were under greater oxidative stress.
This work is in its initial stages and much research is required before these sensors can be readyfor medical use. But these findings reveal the potential of such technology. Dr. Bakalova notes:“Our sensor is suitable for analyzing even small redox imbalances associated with theoverproduction of ROS, via MRI. And while MRI and CT by themselves have been able todiagnose advanced stage kidney damage, they have not yet been able to visualize early stagesof dysfunction. The use of our probe could help clinicians identify patients in the early stage ofrenal damage before they need hemodialysis or kidney transplantation. With further research,
our sensor could be the next generation of redox-sensitive contrast probes for early diagnosisof kidney dysfunction, and perhaps, a number of other diseases that are accompanied byinflammation.”2

Left: Schematic illustration of the novel chemical sensor. In its oxidized state, it releases a magnetic signal
measurable with EPR or MRI, and in its reduced state, it releases a fluorescence signal measurable withfluorescence imaging. Right: Demonstration of the novel sensor’s diagnostic utility. The magnetic signals fromkidneys in mice fed a high-cholesterol diet (B) are much stronger than the magnetic signals from the sensors inhealthy mouse kidneys (A). This suggests that the high-cholesterol diet induces oxidative stress in the kidneys.
Picture credits: National Institutes for Quantum and Radiological Science and Technology###Research Article“Quantum Sensors To Track Total Redox-Status and Oxidative Stress in Cells andTissues Using Electron-Paramagnetic Resonance, Magnetic Resonance Imaging, andOptical Imaging“
Dessislava Lazarova, Severina Semkova, Genoveva Zlateva, Higashi Tatsuya, Ichio Aoki,and Rumiana Bakalova“Analytical Chemistry “: January 28, 2021, DOI: https://doi.org/10.1021/acs.analchem.0c04116

About National Institutes for Quantum and Radiological Science and Technology
The National Institutes for Quantum and Radiological Science and Technology (QST) wasestablished in April 2016 to promote quantum science and technology in a comprehensive andintegrated manner. QST’s mission is to raise the level of quantum and radiological sciences
and technologies through its commitment to research and development into quantum scienceand technology, the effect of radiation on humans, radiation emergency medicine, and themedical use of radiation. To ensure that research and development delivers significant
academic, social and economic impacts, and to maximize benefits from global innovation, QST
is striving to establish world-leading research and development platforms and explore newfields.
Website: https://www.qst.go.jp/site/qst-english/

3About Dr. Rumiana Bakalova (Chief researcher, QST)
Rumiana Bakalova graduated from the Sofia University “St. Kliment Ohridski” Faculty ofBiology with a specialization in biochemistry. She received her Ph.D. degree in 1990 at theBulgarian Academy of Sciences and a D.Sc. degree in 2011 at the Sofia University “St. KlimentOhridski”. She is currently associated with the National Institutes of Quantum and Radiological
Science and Technology, Japan. She is an avid researcher of redox-related molecularmechanisms underlying cancer and their potential as therapeutic targets. To date, she has over
200 publications in prestigious journals, such as Nature Biotechnology, Nature Photonics, TheLancet, Nano Letters, Clinical Cancer Research and others, to her name, as well as 11 patents.
Funding information
This study was funded by the Japanese Society for the Promotion of Science (Grant-in-Aid-C),
the Japanese Agency for Medical Research and Development (Next-generation Cancer therapy[P-CREATE]), and the Japanese Science and Technology Agency (Center of InnovationProgram).
Media contact:
Public Relations Section
Department of Management and Planning, QST
Tel: +81-43-206-3026 Email: info@qst.go.jp

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