title: Development of an antibody-based, modular biosensor for 129Xe NMR molecular imaging of cells at nanomolar concentrations.
abstract: Magnetic resonance imaging (MRI) is seriously limited when aiming for visualization of targeted contrast agents. Images are reconstructed from the weak diamagnetic properties of the sample and require an abundant molecule like water as the reporter. Micromolar to millimolar concentrations of conventional contrast agents are needed to generate image contrast, thus excluding many molecular markers as potential targets. To address this limitation, we developed and characterized a functional xenon NMR biosensor that can identify a specific cell surface marker by targeted (129)Xe MRI. Cells expressing the cell surface protein CD14 can be spatially distinguished from control cells with incorporation of as little as 20 nM of the xenon MRI readout unit, cryptophane-A. Cryptophane-A serves as a chemical host for hyperpolarized nuclei and facilitates the sensitivity enhancement achieved by xenon MRI. Although this paper describes the application of a CD14-specific biosensor, the construct has been designed in a versatile, modular fashion. This allows for quick and easy adaptation of the biosensor to any cell surface target for which there is a specific antibody. In addition, the modular design facilitates the creation of a multifunctional probe that incorporates readout modules for different detection methods, such as fluorescence, to complement the primary MRI readout. This modular antibody-based approach not only offers a practical technique with which to screen targets, but one which can be readily applied as the xenon MRI field moves closer to molecular imaging applications in vivo.
authors: European Research Council (ERC) Project BiosensorImaging, Department of Structural Biology, Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany; and.
authors: Honor M
authors: HM
authors: Rose
authors: European Research Council (ERC) Project BiosensorImaging, Department of Structural Biology, Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany; and.
authors: Christopher
authors: C
authors: Witte
authors: European Research Council (ERC) Project BiosensorImaging, Department of Structural Biology, Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany; and.
authors: Federica
authors: F
authors: Rossella
authors: European Research Council (ERC) Project BiosensorImaging, Department of Structural Biology, Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany; andDepartment of Biochemistry, Institute for Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
authors: Stefan
authors: S
authors: Klippel
authors: Department of Biochemistry, Institute for Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
authors: Christian
authors: C
authors: Freund
authors: European Research Council (ERC) Project BiosensorImaging, Department of Structural Biology, Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany; and lschroeder@fmp-berlin.de.
authors: Leif
authors: L
authors: Schröder
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells; D055592:Biophysical Phenomena; D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods* / Q000706:statistics & numerical data; D002460:Cell Line; D003287:Contrast Media; D007091:Image Processing, Computer-Assisted; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000706:statistics & numerical data; D051379:Mice; D057054:Molecular Imaging; D041681:NIH 3T3 Cells; D036103:Nanotechnology; D011083:Polycyclic Compounds / Q000737:chemistry; D059629:Signal-To-Noise Ratio; D014979:Xenon Isotopes
chemical_list: D003287:Contrast Media; D018950:Lipopolysaccharide Receptors; D011083:Polycyclic Compounds; D014979:Xenon Isotopes; C545484:cryptophane A
keywords: spin hyperpolarization; targeted imaging