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

• Published in: Angewandte Chemie International Edition 2014-01, Vol.53 (2), p.493-496
• Main Authors: Klippel, Stefan, Döpfert, Jörg, Jayapaul, Jabadurai, Kunth, Martin, Rossella, Federica, Schnurr, Matthias, Witte, Christopher, Freund, Christian, Schröder, Leif
• Format: Article
• Language: English
• Subjects: Animals; Biosensing Techniques - instrumentation; Biosensing Techniques - methods; Cages; cell tracking; Cell Tracking - instrumentation; Cell Tracking - methods; Cellular; Contrast Media - chemistry; Equipment Design; Fluorescein - chemistry; Fluorescence; host-guest systems; hyper-CEST; Magnetic resonance imaging; Magnetic Resonance Imaging - instrumentation; Magnetic Resonance Imaging - methods; NMR; NMR imaging; Nuclear magnetic resonance; Polycyclic Compounds - chemistry; Position (location); Sensitivity and Specificity; Signal-To-Noise Ratio; Tracking; Xenon; Xenon - chemistry
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201307290

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. Xenon, the crypt keeper: Cryptophanes (CrA) are introduced as xenon hosts for live‐cell MRI with fluorescence co‐registration. Cellular uptake of the lipophilic cages, as identified by a unique chemical shift, is read‐out using hyperpolarized 129Xe and chemical exchange saturation transfer. Localization of labeled cells is achieved with a single acquisition at low micromolar CrA concentrations, thus demonstrating very sensitive MRI cell tracking with switchable contrast.