Molecular Sensing Using Hyperpolarized Xenon NMR Spectroscopy

Molecular imaging is the determination of the spatial location and concentration of specific molecules in a sample of interest. Sophisticated modern magnetic resonance imaging machines can collect NMR spectra from small‐volume elements within a sample, enabling local chemical analysis. However, abundant water and fat signals limit detection of metabolites to near m M concentrations. Alternatively, targeted relaxation contrast agents enhance the relaxation of the strong water signal where they bind. A comparison of images with and without a contrast agent shows the target distribution, but high µ M concentrations are needed. We have developed an approach that exploits the strong signals of hyperpolarized 129 Xe (an inert reporter introduced for imaging). The imaging contrast agents are composed of a biological recognition motif to localize the agent (antibodies or aptamers) and covalently tethered cryptophane cages. Xenon binds to the cryptophane and though chemical exchange saturation transfer creates contrast in a xenon image. Imaging agents can deliver many cages per target, giving detection limits in the p M concentration range. The evolution and principles of this approach are described herein.