Katarzyna Benkosz, Wprost: PET: Positron emission tomography is a modern diagnostic method that involves examining the emission of positrons: particles that are formed after the decay of radioactive isotopes. When the test shows increased metabolism and accumulation of isotope-labeled molecules in cells, this may indicate, for example, cancer. PET diagnostics are still new in medicine, but you have been collaborating for years with the team of Prof. Paweł Moskal, who has developed a new type of PET. The prototype was already tested at the Jagiellonian University Hospital a few months ago. Will Jagiellonian PET (J-PET) revolutionize medicine?
Professor Ewa Stepin: This is a revolutionary solution for several reasons. First of all, it is made of plastic and polymers: a new material that has never been used before to build CT scanners. Conventional CT scanners are made of crystalline materials. A CT scanner made of plastic scintillators would significantly reduce the cost of CT, which would contribute to increasing the availability of this type of examination to patients. It would also be much lighter.
The second revolutionary change in medicine is that this CT scan can be used to analyze other parameters that have not been discovered and analyzed in PET scans until now: this other parameter is the positronium lifetime parameter.
How old is positronium and positronium?
Let’s start with how “conventional” PET works: the phenomenon detected with positron emission tomography (PET) is the annihilation of positrons and electrons: the place where they combine and decay is detected, creating photons that are detected by PET. It is possible to determine where this radiation is emitted, i.e., where the cancer process may have occurred. This is sufficient for metabolic imaging, which is often used to diagnose cancer. For example, a patient is given radiofluorescently labeled glucose; in tissues where more radiofluorescently labeled glucose accumulates, the signal is stronger, which means that it is possible to determine the location of a lesion, such as a cancer, accompanied by the accumulation of radiopharmaceuticals.
A new parameter that we can check thanks to J-PET is the lifetime of positronium. It allows us to determine how long the annihilation process of the positron and electron takes, that is, how long the atom formed as a result of the combination of the positron and the electron “lives”. Physicists call it the “strange atom”. Or in other words – positronium. It can “live” shorter or longer, and the time here is measured in nanoseconds and picoseconds. The lifetime of positronium depends on the environment in which it is created, and this can be influenced by metabolism, oxygen concentration, and above all, the structure of tissues at the nano level, that is, the size of molecules that we have not yet studied.
This additional parameter – the positronium lifetime – has not been studied until now because there was no such possibility – the appropriate equipment, but also the appropriate isotopes that would allow testing the positronium lifetime. Research on this phenomenon was initiated by Prof. Paweł Moskal 15 years ago at the Faculty of Physics of the Jagiellonian University. And we have been conducting clinical trials for more than two years. The first experiment was carried out in March 2022 at the Medical University of Warsaw, where we measured the positronium lifetime in a patient. It was a patient with a glioma of the brain. Our article will soon be published in the prestigious journal Science Advances, where we describe this research.
What clinical significance could testing this new parameter have for a patient? What more can you see with this?
The clinical significance remains to be seen, and clinical trials are necessary. We conducted a second clinical trial at the University Hospital in Krakow this year – the data are currently being analyzed.
With conventional PET, we can only determine the accumulation of radiopharmaceuticals in a specific location. With J-PET and positronium lifetime testing, we will also be able to know the molecular composition of the tissue. In the case of a cancerous tumor, the tissues are different, the tumor produces different proteins, and there is a different metabolism.
Will you be able to see cancer tissue better?
It is better to distinguish it from healthy tissue. We expect that we will be able, for example, to assess the degree of oxidation, that is, the concentration of oxygen: thanks to this we will know what the metabolism of the cancerous tumor is. This is of great clinical importance because, for example, cancers that suffer from hypoxia (lack of oxygen) do not respond well to treatment; they are more resistant to anticancer treatments. We will be able to see better the stage of the tumor and where it comes from and assess the patient’s response to treatment.
J-PET can also be used in diseases other than cancer. For example: neurodegenerative diseases, which involve structural changes in brain tissue. They are visible on MRI, but we would like to see them early, when they are already visible on the molecular level – the possibility of using positronium lifetime could contribute to this.
This could be an additional feature indicating the stage of cancer development, for example, or the extent of structural change in the tissue: until now, this has not been possible to image. Based on the positronium lifetime, PET diagnostics could be extended to other diseases and their stage of progression could be better distinguished.
By making J-PET from plastic materials, will the device be cheaper and therefore more accessible?
The CT will be made of plastic scintillators – this significantly reduces the cost. It will also be possible to build a large CT, which will make it possible to image the entire patient. Currently, when a CT scan is performed – regardless of whether it is a CT scan, i.e. so-called X-ray CT, MRI or PET – only part of the body is examined. If we want to image the entire patient, we will need to perform several scans. The plastic J-PET could serve as a “large bed” – somewhat reminiscent of a sunbed – in which it will be possible to “scan” the entire patient at once. This is extremely important: until now, it was not possible to imagine how quickly radiopharmaceuticals could be distributed throughout the entire body, and we could only see them in a specific part of the body. Thanks to J-PET, the sensitivity of the imaging increases significantly, making it possible to “see” the entire patient while administering lower doses of radiopharmaceuticals.
Lower doses of radiopharmaceuticals also mean greater safety for patients?
Yes, although I must point out right away that the use of radiopharmaceuticals in the case of a PET scan is safe, otherwise the test would not be performed. It is a very large dose at a time, but the radiopharmaceutical breaks down quickly.
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However, the radiopharmaceuticals themselves are expensive, and the lower dose also reduces the cost of the test. Thanks to J-PET and its plastic structure, the cost of producing the device itself is lower, as is the cost of using the radiopharmaceuticals.
As I mentioned, J-PET will be able to image the patient’s entire body. Of course, we are not the only center in the world that is researching the creation of this type of PET; work is currently underway to create PET images that can image the entire body; then we are talking about imaging the entire body – the total body. This is very important, for example, when diagnosing cancer metastases, but also when diagnosing other diseases – such as inflammation, autoimmune diseases and complications of infections. There could be more diseases that could be diagnosed using total body imaging. There could also be greater accessibility for patients if there were more and cheaper CT scanners.
All this shows how important the collaboration of physicians with physicists and molecular biologists is to medicine?
As the head of the Department of Medical Physics, I must say that medical physics is a very important and rapidly developing field of medicine. We have few medical physicists in Poland, but they are very necessary, even indispensable.
Is this the profession of the future?
I have been involved in medical imaging for more than 20 years, and I see a huge technological breakthrough: PET and J-PET are examples of this. Another breakthrough is the use of artificial intelligence to support the analysis of images obtained by tomography, including positron emission tomography (PET). Medical physics is also essential for personalized therapy. We are increasingly talking about a comprehensive approach to diagnosis and treatment – theranostics. This means diagnosis and treatment, most often in the case of cancer. Radioisotopes are used to quickly localize the lesion, while other radioisotopes destroy cancer cells. This is the future direction of medical physics and medicine. Therefore, I would strongly encourage young people who are thinking about choosing a field of study and who are interested in medicine and exact sciences to choose medical physics: it is a very promising profession.
Back to the J-PET clinical trials: when can we expect their results, and above all, will this scientific revolution turn into a clinical revolution?
The clinical trials I mentioned were conducted in April and May of this year, of course with the approval of the Bioethics Committee. 25 patients with various cancers were examined. We already have the first analyses that allow us to compare the images obtained from conventional CT and the prototype J-PET. After the routine PET scan, the patient was transferred to the J-PET bed for a few minutes. It was not necessary to administer additional radiopharmaceuticals; we used radiation from an isotope that is administered for routine PET. The clinical trial is now complete, we are analyzing the results, they are very promising, and we are currently preparing a publication on the subject. The entire technology is, of course, patented, patented by Professor Pawel Moskal at the Jagiellonian University. Of course, further work is underway to use J-PET, including: the Technology Transfer Center of the Jagiellonian University, but further clinical trials and then production are necessary.
Our first positronium images have aroused great interest around the world. There are already several centers and companies working on the introduction of positronium lifetime coefficients into research. We also cooperate scientifically with several foreign centers. However, we hope, above all, that Polish technology will find application and serve patients.
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