Oxygenation maps of tumors

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Since the early days of medicine, doctors have wanted to look inside the human body in order to understand the functioning of the internal organs and to find ways to treat their disorders. Today, this dream has come true – we are able to know the detailed structure of internal organs. Is there a need to develop any other new imaging techniques?

Ultrasonography enables future parents to watch the features of their baby's face even before it is born. Radioisotopes and PET (positron emission tomography) imaging allow us to detect the location of cancer metastases throughout the body. We have a wide range of non-invasive ways to collect information about the inside of the human body at our disposal. Is it necessary to constantly search for new, even more advanced diagnostic techniques?

Important phenomenon: hypoxia

One of the fields where such need still exists, in spite of the achievements mentioned above, is oncology. As a result of a high level of metabolism and a pathological, incapable network of blood vessels, cancerous tumors suffer from lack of nutrients and oxygen. Insufficient level of oxygenation (hypoxia) of cancerous tissue impairs the tumors' response to therapy. Hypoxia also leads to more aggressive behavior of the tumor – it enhances the survival capability of cancer cells, their ability to adapt to difficult conditions and to create metastases.

Hypoxia is a term describing an insufficient level of oxygen in the tissue, which usually arises due to inadequate oxygen supply.

"My fascination with oxygen started in the seventh grade, when I read a small, popular science book about the functioning of mitochondria. It described how the electrons jump between subsequent elements of the breathing chain, ending at molecular oxygen. This molecule, which is fundamental for life, is the subject of my research today," says Martyna Elas, PhD, from the Jagiellonian University's Faculty of Biochemistry, Biophysics and Biotechnology.

Molecular oxygen is present in all cells of our bodies. It is a paramagnetic, as it contains unpaired electrons and thus in the presence of a magnetic field it behaves like a small magnet. If there is another paramagnetic molecule in the proximity of an oxygen molecule, they will interact with each other. This phenomenon enables us to detect oxygen with the use of electron paramagnetic resonance spectroscopy (EPR). This method allows us to "see" molecules with unpaired electrons. Similarly to the magnetic resonance method, for the test to be effective, the object has to be placed in a magnetic field. Moreover, just like magnetic resonance imaging, EPR also enables us to obtain three-dimensional images of living objects. The introduction of a non-toxic probe into the body and recording its signal in a three-dimensional reference system leads to the creation of spatial oxymetric maps (showing the concentration of oxygen in specific parts of the body). This approach is used by several groups of scientists working on non-invasive oxymetric imaging of the heart, brain, tumors and other tissues.

Sample cross-section of an oxygenation map
of a mouse leg with a tumor (outlined in black).
Thickness of the cross-section 0.6 mm, image
length 21 mm. The imaging time was approx.
10 minutes. The image was obtained at the Center
for EPR Imaging in vivo Physiology, University of Chicago


Oxygen tells us how to cure

In co-operation with Howard Halpern, MD, PhD from the University of Chicago, who is developing EPR imaging with the intention to introduce the application of this method in patients, scientists from the Jagiellonian University analyzed oxygen maps of tumors in the context of radiotherapy. With the use of EPR imaging in mice, oxymetric maps of tumors before and after radiation therapy were obtained. Single, quite high doses of radiation were used in the experiments, which led to curing most of the tumors within a few weeks. For 90 days following the therapy scientists checked whether there was a recurrence of the tumor's activity. A total of 18 out of 34 mice that were subject to therapy remained healthy after three months. The most important finding was the fact that the oxygenation of the tumors prior to therapy helped to determine which tumors would be cured. If there was very little oxygen in the tumor, the dose of radiation required to cure it was high. Conversely, if the oxygenation of the tumor was slightly higher, the dose could be a little lower.

The research has proven that EPR imaging is useful in radiation therapy and that it may be used in order to improve the efficiency of this type of treatment. Moreover, EPR oxymetric maps tell us not only how much oxygen there is in the tissue but also in which parts of the tumor it is located. In the future this might allow for an individual approach to therapy for each patient, which will lead to an optimum selection of the radiation dose.

Apart from oncology, oxymetric maps may be useful in the therapy of other pathological conditions connected with insufficient oxygenation, such as cardiovascular diseases, stroke or wound healing.

Research team from the Faculty of Biochemistry, Biophysics and Biotechnology: Martyna Elas, PhD; Martyna Krzykawska-Serda, PhD; Katarzyna Jasińska, MSc; Michał Gonet, MSc; Agnieszka Drzał, MSc