Novel Molecular Tags Permit More Versatile Bioimaging

A new study describes a class of molecular tags that enhance magnetic resonance imaging (MRI) signals, and could enable widespread real time monitoring of metabolic processes in cancer and heart disease.

Researchers at Duke University (Durham, NC, USA) have succeeded in developing a cost-efficient method to directly hyperpolarize long-lived nuclear spin states on universal 15N2-diazirine molecular tags. Named SABRE-SHEATH, the technique results in a higher than 10,000-fold enhancement in the generation detectable nuclear MR signals, that can also last much longer. The 15N2-diazirines are biocompatible, inexpensive to produce, and can be incorporated into a wide range of biomolecules without significantly altering molecular function.

Current hydrogen-based hyperpolarization techniques result in agents visible for only seconds, and thus cannot monitor the majority of biological processes. The 15N2-diazirine molecular tags, on the other hand, are composed of two nitrogen atoms bound together in a ring, a geometry that traps hyperpolarization in a state that does not relax quickly, thus greatly enhancing magnetic resonance signals for over an hour. An added advantage is that it can be tagged on small molecules, macro molecules, and amino acids, without changing the intrinsic properties of the original compound. The study was published in the March 25, 2016, issue of Science Advances.

“This represents a completely new class of molecules that doesn't look anything at all like what people thought could be made into MRI tags,” said senior author Professor Warren S. Warren, PhD, chair of Physics at Duke. “We envision it could provide a whole new way to use MRI to learn about the biochemistry of disease. In a minute, you've made the hyperpolarized agent, and on the fly you could actually take an image. That is something that is simply inconceivable by any other method.”

The hyperpolarized state is a very low spin temperature state that is not in a thermal equilibrium with the temperature of the sample. Low spin temperature leads to high magnetization of the spin ensemble, resulting in very high nuclear MRI signal. This spin state eventually returns to the thermal equilibrium temperature (depolarization).

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