Credit: © 2008 ACS

The clinical use of magnetic resonance imaging (MRI) to examine biological tissue has so far been restricted to proton-NMR techniques. Recent reports on the risks of using contrast agents such as gadolinium — used to improve the images acquired — have motivated research on non-proton MRI techniques. Xenon that has been 'hyperpolarized' — pre-treated to induce a non-equilibrium distribution of polarized nuclei and thus enhance the signal — has previously been shown to be a possible alternative. It can also be caged within a cryptophane molecule, offering opportunities for further functionalization to create biosensors with specific targets.

Ivan Dmochowski and colleagues from the University of Pennsylvania and the University of Rochester have now studied1 the interactions of 129Xe biosensors with two isozymes of carbonic anhydrase — CAI and CAII — that have been implicated in the formation of certain tumours and kidney diseases. The biosensor consists of a xenon atom trapped within a cryptophane cage that is functionalized with a biological recognition motif that will bind to the carbonic anhydrase.

The length of the enzyme-binding ligand was systematically altered to study how interactions between the biosensor and carbonic anhydrase influence the NMR shifts. The NMR spectra of the biosensor–CA complexes reveal peaks of narrow linewidth that are shifted with respect to the unbound biosensor. These shifts are larger than those seen in any previously studied xenon biosensing system, thus improving the resolution of the technique. The spectra also make it possible to discriminate between CAI and CAII because of the very large differences in their respective chemical shifts when they are bound to the biosensor.