Molecular Sensing Using Hyperpolarized Xenon NMR Spectroscopy

• Published in: Israel journal of chemistry Vol. 54; no. 1-2; pp. 104 - 112
• Main Authors: Palaniappan, Krishnan K., Francis, Matthew B., Pines, Alexander, Wemmer, David E.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.02.2014; WILEY‐VCH Verlag; Wiley Subscription Services, Inc; Wiley
• Subjects: Cages; Contrast agents; Exchange; Image contrast; Imaging; imaging agents; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; magnetic properties; Magnetic resonance imaging; natural products; NMR spectroscopy; Target detection; Xenon
• ISSN: 0021-2148; 1869-5868
• DOI: 10.1002/ijch.201300128

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 mM 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 µM concentrations are needed. We have developed an approach that exploits the strong signals of hyperpolarized 129Xe (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 pM concentration range. The evolution and principles of this approach are described herein.