Oxygen maps of tumors

Diagnostic help for cancer treatment

Doctors have always been curious to look inside the human body, to understand how different organs work and find solutions to their malfunction. Today this dream has been more than fulfilled. We are able to see minute structural details using magnetic resonance imaging; prospective parents can see the facial expressions of their baby inside the womb using ultrasonography; and distant metastases can be scanned for within the whole body using radionuclides and PET scans. A vast array of imaging methods and approaches is available to gather this information from the inside of the human body in a non-invasive way. So, do we really need to develop new imaging techniques?
One of the areas where such a need arises is in cancer therapy. Tumors are starved for nutrients as well as for oxygen, due to their intensive metabolism and pathologic blood supply. The absence of adequate oxygen levels in tissue, known as hypoxia, limits the responsiveness of tumors to therapies. Hypoxia also leads to more aggressive tumor behaviour - enhancing the ability of tumor cells to survive, to adapt to harsh conditions and to metastasize.

My fascination with oxygen started when at the age of 13 I came across a small popular science book which described the jumping of electrons within the mitochondria, making their final jump to a molecule of oxygen. That same molecule, so crucial to life, is the focus of my work today. Molecular oxygen, present in all the cells of our body, is a paramagnetic - that is, it contains unpaired electrons and therefore behaves as a small magnet in the presence of a magnetic field. If another paramagnetic molecule happens to be in the vicinity of the oxygen molecule, they interact. This particular feature makes oxygen detectable by Electron Paramagnetic Resonance (EPR) spectroscopy. EPR enables us to "see" molecules with unpaired electrons. Similarly to magnetic resonance, it requires the samples to be placed within a magnetic field, and also in parallel to magnetic resonance it is possible to obtain three-dimensional images of live objects. Introducing a non-toxic oxygen spin probe into an animal and registering the signal of the spin probe within the three-dimensional space gives us an oxygen map of the studied animal. Such an approach is being applied by several groups of scientists developing non-invasive oxygen imaging of heart, brain, tumors and other organs.

In collaboration with Dr Howard Halpern from the University of Chicago, who is developing low-frequency EPR imaging of tumors with the goal of introducing it into the clinic, we have studied oxygen maps in the context of radiotherapy of tumors. Mice with tumors were first imaged using EPR. The tumors were then irradiated with a high, single dose of X-rays. After such high doses, most of the tumors disappeared completely within a couple of weeks. For the next 90 days the mice were carefully monitored to observe if any regrowth occurred. Out of 34 animals in this study, 18 remained cured after three months. The crucial thing we demonstrated was that oxygenation of tumors before the treatment was helpful in predicting the result of the therapy. If an animal demonstrated low oxygenation of the tumor, the dose required to cure was high; and if oxygenation of the tumor was slightly higher, the dose could be a little lower. We have shown that information from EPR images is useful in radiotherapy, and can be used in future to enhance the effectiveness of this cancer treatment. What is more, EPR oxygen maps provide information not only on how much oxygen is there, but also where the regions with low oxygenation are located. This may allow more individualized radiotherapy treatment in the future, tailored for a particular patient, with increased doses delivered to hypoxic regions.

EPR imaging provides three-dimensional oxygen maps of tumors, giving a non-invasive insight into tumor physiology. Oxygen mapping may also enhance the effectiveness of radiotherapy, identifying hypoxic regions in tumors for a selective radiation dose increment. Apart from cancer therapy, these oxygen images are currently being investigated in other pathologies related to oxygen depletion, such as cardiovascular diseases, stroke, or wound healing. (Martyna Elas, Jagiellonian University in Krakow, www.atomiumculture.eu)

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