Xenon magnetic resonance imaging: making pathological changes in the body visible

As an imaging procedure, magnetic resonance tomography has become essential in clinical practice, since it can easily make organs and tissue visible. However, until now abnormal cancer cells or small centers of inflammation remained almost invisible. Now cell biologists from Berlin, Germany, have succeeded in fixing this problem with xenon magnetic resonance imaging.


Photo: Dr. Leif Schröder

Dr. Leif Schröder; ©David Ausserhofer

In this interview with MEDICA.de, Dr. Leif Schröder from the Leibniz Institute for Molecular Pharmacology (FMP) explains how xenon magnetic resonance imaging is not just applicable in medicine, but also in other areas.

Dr. Schröder, how does xenon magnetic resonance imaging work?

Leif Schröder: Xenon magnetic resonance imaging is a particular advancement of traditional magnetic resonance tomography. It uses so-called hyperpolarized xenon, a harmless noble gas combined with a special contrast agent to create a stronger signal. To do this, the xenon atoms are modified in their magnetic properties in a laser machine to where it becomes possible to create a very strong signal with relatively few atoms.
During the next step, the xenon atoms need to be connected to specific cell structures. We managed to accomplish this step with a type of modular system, in whose development the task force of Christian Freund at the Free University of Berlin was instrumental.
Here the cryptophane molecules, which are a component of the administered contrast agent, bind the xenon atoms. The xenon is temporarily being locked up in this cryptophane cage as it were. It represents the link between a molecular target – a receptor on the cell surface for example – and the xenon, which is ultimately being detected. The cage in turn can be easily used as a probe in the human body. The cryptophane ties to disease-specific markers on the cell surface. The temporarily trapped xenon in the cage then resonates with the radio waves. We were also able to create bi-color signals by adding an alternative to the cages. The xenon subsequently responds to radio waves in a different frequency, so that some cells are depicted in green and others in red color.
Xenon magnetic resonance imaging can therefore be used for very specific diagnostics, which is not possible with other MRI contrast agents, since it can be specifically developed for different markers.

What does an examination look like using this process?

At first, the contrast agent that specifically binds to the marker is being administered. After a while, it accumulates in the abnormal tissue. Compared to the conventional method, you then need to additionally administer the xenon. This can be done in two different ways. One way is to administer the xenon by inhalation. The patients would then need to inhale a gas mixture that partially contains xenon. Alternatively, you can dissolve the xenon ahead of time in certain substances such as blood plasma that is being injected, so it is immediately available in the bloodstream.

Photo: Dr. Leif Schröder (right) und Honor Rose (left) im Labor

Honor Rose and Dr Leif Schröder are preparing their experiments in the cell culture lab. Schröder is holding a model of a cryptophane cage in his hands; © Leif Schröder/FMP

What is the cost of gearing such a modular system to a specific marker?

We have significantly reduced costs by using this modular system. In the past, you had to fasten the binding unit that would bind to a specific receptor or via an antibody to an antigen for example, with high chemical input to the cryptophane cages. This modular system simplifies this process. We practically have a central puzzle piece.

What disease-specific changes does xenon magnetic resonance imaging make visible?

Essentially anything that can be detected with an antibody, for instance membrane proteins that are specific for cancer cells. Another promising application would be the labeling of atherosclerotic plaques. Currently we are developing a sensor that works specifically for breast cancer. By using the contrast medium, you could also assess ahead of time whether a treatment with specific drugs would make sense or not.

Does this mean that aside from imaging procedures, xenon magnetic resonance imaging could also be used as a tracking system for drugs?

Together with the task force surrounding Margitta Dathe, we have packed the used molecular probes into tiny liposomes. We essentially used the empty packages and added a tracking system to them to conduct a kind of package tracking so to speak. One aspect of the work by the Dathe group is to develop these liposomes in such a way to where they can ultimately also be loaded with active ingredients and released at specific target structures. If you combine this with imaging, you could see where these so-called carrier systems are in the body at any point in time. In doing so, you would essentially have a tracking option.
Another rather accidental examination spectrum resulted when we decided to connect our method for new contrast agents with Margitta Dathe’s experience as far as labeling blood-brain barrier cells is concerned. Efforts to make damages in the barrier visible through diagnostic imaging systems have been there for quite some time. The result was that we are indeed able to label blood-brain barrier cells. This is of high diagnostic value, because we know that the blood-brain barrier changes for certain diseases. You could then retrace, whether it is still intact.

How far away is clinical application of xenon magnetic resonance imaging?

We consider feasibility studies in animal models as the next step. Everything else is hard to assess. An approval process from preclinical to clinical application is a very time-consuming matter for such an entirely new method, but we are working towards it in the long run. At a certain point in time, you would then have to look for a partner in the industry, who agrees to market this product. At that point you would have to decide how detailed the development should be. Do you develop a contrast agent that is specific for every type of cancer or are there specific possible combinations to keep the approval procedure somewhat manageable? I believe there are also sufficient approaches in animal diagnostics, since pharmaceutical companies have adequate need for tests of new drugs. You could also provide the desired effects in this area by using imaging.
Photo: Melanie Günther; Copyright: B. Frommann

©B. Frommann

The interview was conducted by Melanie Günther and translated from German by Elena O'Meara.