Xenon biosensors for multi-purpose molecular imaging

Hyperpolarized xenon is an exquisite NMR probe for sensing molecular environments of the noble gas in solution. By trapping it in molecular cages like cryptophane-A, ¹²⁹Xe can report information about molecular-specific binding events or resolve multiple signals simultaneously from different micro-environments in a lipid emulsion-a macroscopically- homogeneous phase that mimics properties of biological relevance. The Hyper-CEST detection scheme can be used in this context to pair significant signal enhancement with high specificity of xenon NMR resonances. Hyper-CEST can reduce the measurement time by a factor of up to 16 million and is currently able to detect biosensor concentrations as low as 1.4 nM. When combined with highly frequency-selective pulses, it also allows for demonstration of multiplexing potential using a single cage type as contrast agent for different environments in NMR imaging. This molecular imaging approach enables a switchable contrast that includes also temperature-sensitive imaging with molecular sensors that can be functionalized with various targeting molecules to bind, e.g., specifically to receptors of cancer cells.