New Contrast Media for Deep Insights

Researchers at the Helmholtz Zentrum München, in collaboration with colleagues from the Technical University of Munich (TUM), have developed two molecular sensors that allow them to see changes in the concentrations of the important signaling molecule calcium inside the body. Two publications in the journal ‘Analytical Chemistry’ describe the new options that could be put to use in various medical fields.

molecular sensors
When calcium binds to the hyperpolarized molecule, it changes the frequency at which the molecule resonates in MRI, similar to the way a tone sounds on a string instrument. Source: Barth van Rossum, Reprinted with permission from Mishra, A. et al.: Hyperpolarized Multi-Metal 13C‑Sensors for Magnetic Resonance Imaging. Analytical Chemistry, doi: 10.1021/acs.analchem.6b03039. Copyright 2016 American Chemical Society.

When physicians and scientists want to examine living tissue without opening up the body, they turn to modern imaging methods. The penetration depth is often limited, however, because after a certain distance, strong scattering of light causes a loss of signal.

Advances can be achieved by means of improved measuring instruments as well as corresponding responsive contrast agents, which translate biological processes into suitable signals that the scientists can read out. Under the supervision of Prof. Dr. Gil Gregor Westmeyer, a team at the Helmholtz Zentrum München with first authors Dr. Anurag Mishra and Dr. Giorgio Pariani has now described two new molecular sensors in the two papers. In the future, using these sensors in magnetic resonance imaging and optoacoustic imaging should make it possible to observe changes in the concentrations of the central signal molecule calcium deep inside the tissue.

In optoacoustic (or photoacoustic) imaging, laser pulses locally heat the target area, which causes a short-term expansion of the tissue leading to ultrasonic signals. The scientists then acquire these signals with an appropriate transducer and ‘translate’ them into three-dimensional images – without any radiation exposure. “It took a trick to make calcium molecules visible, which for example enter nerve cells during neuronal activity,” explains study leader Westmeyer. “We were able to develop a molecule that selectively binds to calcium ions and then changes its color – its absorption spectrum,” the scientist continues. “This molecule ensures that we always see a signal change on the screen when the calcium concentration changes.”

The scientists also see great promise for their second molecule: This is also a binding partner for metal ions, but its structure and possible applications differ. “We use a somewhat more complex procedure for this approach,” explains study leader Westmeyer. “The molecule that we use is labeled with C13 carbon atoms and is additionally hyperpolarized before use.” The doctor uses this term to describe a procedure that is used for synchronization of nuclear spins, which then leads to especially strong signals in magnetic resonance imaging (MRI). When calcium binds to the hyperpolarized molecule, it changes the frequency at which the molecule resonates in MRI, similar to the way a tone sounds on a string instrument. Zinc, another biomedically important metal ion that, for example, is released along with insulin, generates a different tone. “The hyperpolarization of the new contrast media sensor allows us to increase the visibility of calcium and similar ions by a factor of ten to a hundred,” Westmeyer explains the improvement. “We think that cardiovascular and neuroscientific research are two possible fields of application.”