title: Cell tracking with caged xenon: using cryptophanes as MRI reporters upon cellular internalization.
abstract: 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 10(3) -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.
authors.affiliation: ERC Project BiosensorImaging, Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125 Berlin (Germany) https://www.fmp-berlin.de/schroeder; Protein Biochemistry Group, Freie Universität Berlin, 14195 Berlin (Germany).
authors.forename: Stefan
authors.initials: S
authors.lastname: Klippel
authors.forename: Jörg
authors.initials: J
authors.lastname: Döpfert
authors.forename: Jabadurai
authors.initials: J
authors.lastname: Jayapaul
authors.forename: Martin
authors.initials: M
authors.lastname: Kunth
authors.forename: Federica
authors.initials: F
authors.lastname: Rossella
authors.forename: Matthias
authors.initials: M
authors.lastname: Schnurr
authors.forename: Christopher
authors.initials: C
authors.lastname: Witte
authors.forename: Christian
authors.initials: C
authors.lastname: Freund
authors.forename: Leif
authors.initials: L
authors.lastname: Schröder
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods*; D058948:Cell Tracking / Q000295:instrumentation / Q000379:methods*; D003287:Contrast Media / Q000737:chemistry*; D004867:Equipment Design; D019793:Fluorescein / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D011083:Polycyclic Compounds / Q000737:chemistry*; D012680:Sensitivity and Specificity; D059629:Signal-To-Noise Ratio; D014978:Xenon / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D011083:Polycyclic Compounds; C545484:cryptophane A; D014978:Xenon; D019793:Fluorescein
keywords: NMR imaging; cell tracking; host-guest systems; hyper-CEST; xenon