Pumpkin-shaped molecule said to provide ‘stunning’ MRI contrast

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European researchers have discovered a class of molecule that, when exposed to the inert gas xenon, enables MRI contrast significantly sharper than previous contrast techniques.

The contrast-friendly molecules, called cucurbiturils, are shaped like pumpkins and exchange around 100 times more xenon per unit of time than similar molecules.

The study, led by Martin Kunth of the Leibniz Institute for Molecular Pharmacology (FMP) in Berlin, is running as the cover story in the November edition of  Chemical Science.

According to a news release from FMP, the study represents the achievement of the world’s first Xe-MRI images with the cucurbituril molecule—and may lead to offering cancer imaging diagnosticians a sufficient degree of sensitivity to distinguish between different cell types, which differ considerably even within a tumor.

PET-CT can detect small tumor foci and other pathological changes, but the modality does not usually permit differentiation according to cell type, according to FMP.

During the new research, a powerful laser and a vaporized alkali metal were applied to intensify, many times over, the magnetic properties of normal xenon.

The hyperpolarized gas was then introduced into a test solution with “cage molecules,” which temporarily capture the xenon such that a Xe-MRI scan shows the distribution of the xenon in the object.

In a second image, the curcurbituril together with radio waves destroyed the magnetization of the xenon, leading to dark spots on the images.

“It very quickly became clear that cucurbituril might be suitable as a contrast medium," co-author Leif Schröder said in prepared remarks. “However, it was surprising that areas marked with it were imaged with a much better contrast than previously.”

FMP notes that the breakthrough has much to do with speed, as cucurbituril generates contrast “more rapidly than all molecules used to date,” binding the xenon only very briefly.

Also, radio waves are transmitted to detect the inert gas in xenon atoms “within a fraction of a second. In this way, the inert gas is passed through the molecule much more efficiently.”

FMP states that this preclinical trial may come to represent a milestone for cancer diagnostics, as the technique could preclude the need for stressful biopsies.

Further, co-author Dr. Andreas Hennig of Jacobs University Bremen says Xe-MRI “has the great advantage that, in contrast to classical radioactive contrast media, there is no notable radiation exposure for the patient” while cucurbiturils “have proved to be harmless in toxicity tests with mice.”

Lead author Martin Kunth expressed his eagerness to see the discovery of cucurbituril applied to other molecules.

“We will no doubt be able to develop much more sensitive contrast media now, using this approach,” he said in a statement, “and precisely this was the key point in this innovative imaging procedure.”