Cell Tracking with Caged Xenon: Using Cryptophanes as MRI Reporters upon Cellular Internalization

Caged xenon has great potential in overcoming sensitivity limitations for solution‐state NMR detection of dilute molecules. However, no application of such a system as a magnetic resonance imaging (MRI) contrast agent has yet been performed with live cells. We demonstrate MRI localization of cells labeled with caged xenon in a packed‐bed bioreactor working under perfusion with hyperpolarized‐xenon‐saturated medium. Xenon hosts enable NMR/MRI experiments with switchable contrast and selectivity for cell‐associated versus unbound cages. We present MR images with 10³‐fold sensitivity enhancement for cell‐internalized, dual‐mode (fluorescence/MRI) xenon hosts at low micromolar concentrations. Our results illustrate the capability of functionalized xenon to act as a highly sensitive cell tracer for MRI detection even without signal averaging. The method will bridge the challenging gap for translation to in vivo studies for the optimization of targeted biosensors and their multiplexing applications.