Cell labeling with the positive MR contrast agent Gadofluorine M

Department of Radiology, University of California in San Francisco, 505 Parnassus Ave, San Francisco, CA, 94143, USA.
European Radiology (Impact Factor: 4.34). 06/2007; 17(5):1226-34. DOI: 10.1007/s00330-006-0522-9
Source: PubMed

ABSTRACT The purpose of this study was to label human monocytes with Gadofluorine M by simple incubation for subsequent cell depiction at 1.5 and 3 T. Gadofluorine M displays a high r(1) relaxivity and is spontaneously phagocytosed by macrophages. Human monocytes were incubated with Gadofluorine M-Cy at varying concentrations and incubation times and underwent MR imaging at 1.5 and 3 T at increasing time intervals after the labeling procedure. R1-relaxation rates and r1 relaxivities of the labeled cells and non-labeled controls were determined. Cellular contrast agent uptake was examined by fluorescence microscopy and quantified by ICP-AES. Efficient cell labeling was achieved after incubation of the cells with 25 mM Gd Gadofluorine M for 12 h, resulting in a maximal uptake of 0.3 fmol Gd/cell without impairment of cell viability. Fluorescence microscopy confirmed internalization of the fluorescent contrast agent by monocytes. The r1 relaxivity of the labeled cells was 137 mM(-1)s(-1) at 1.5 T and 80.46 mM(-1)s(-1) at 3 T. Imaging studies showed stable labeling for at least 7 days. Human monocytes can be effectively labeled for MR imaging with Gadofluorine M. Potential in vivo cell-tracking applications include targeting of inflammatory processes with Gadofluorine-labeled leukocytes or monitoring of stem cell therapies for the treatment of arthritis.

  • Source
    • "Thus, mannose is replaced by the dye based on a structurally identical attachment. The dye has similar properties in terms of hydrophilicity rendering the Gf-carbocyanine similar to Gf itself (Henning et al., 2007). Gf was applied i.v. at a dose of 0.1 mmol/kg body weight. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Magnetic resonance imaging plays a pivotal role in the diagnosis and treatment monitoring of multiple sclerosis. Currently available magnetic resonance-techniques only partly reflect the extent of tissue inflammation and damage. In the present study, application of the experimental magnetic resonance-contrast agent Gadofluorine M significantly increased the sensitivity of lesion detection in myelin-oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. Gadofluorine M-enhancement on T(1)-weighted (T(1)-w) images utilizing a clinical 1.5 T magnetic resonance unit showed numerous lesions in optic nerve, spinal cord and brain, the majority of which were not detectable on standard T(2)-weighted (T(2)-w) and Gd-DTPA enhanced T(1)-w sequences. Quantitative assessment by pixel counts revealed highly significant differences in sensitivity in favour of Gadofluorine M. Gadofluorine uptake closely corresponded to inflammation and demyelination on tissue sections. These unique features of Gadofluorine M in visualizing inflammatory CNS lesions hold promise for future clinical development in multiple sclerosis.
    Brain 10/2008; 131(Pt 9):2341-52. DOI:10.1093/brain/awn156 · 10.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Die interventionelle kardiovaskuläre Magnetresonanzbildgebung (iMR) ist eine neue Disziplin, die minimalinvasive Therapien ermöglicht und eine attraktive Alternative zu konventionellen röntgengesteuerten kardiovaskulären Interventionen darstellt. Stärken der iMR sind die dreidimen sionale Ortsauflösung und der hervorragende Weichteilkontrast, des Weiteren sind keine ionisierenden Strahlen erforderlich. Für die Durchführung dieser neuen Techniken werden MR-kompatible endovaskuläre Katheter und Instrumente benötigt. Die iMR ermöglicht die gezielte Applikation von Wachstumsfaktoren, Genen oder Stammzellen in Gefäßwände oder in das Myokard sowie endovaskuläre Kathetereingriffe. Die iMR kann mit aktiven und passiven Methoden durchgeführt werden. Die iMR wird in Echtzeit durchgeführt. Endovaskuläre MR-Katheter und Führungsdrähte können sich erwärmen und dadurch zu Sicherheitsrisiken werden. Neuerungen wie offene kurze MR-Tomographen ermöglichen lokale intramyokardiale und intrakoronare Therapieformen. Neue kardiovaskuläre MR-Kontrastmittel tragen zur Verbesserung der iMR-Eingriffe durch Anreicherung in pathologischem Zielgewebe (Myokardinfarkte, atherosklerotische Plaques) bei; darüber hinaus lassen sich die Verteilung, Differenzierung und das Überleben von markierten Stammzellen im Myokard und in Gefäßwänden darstellen. Die iMR-Technik kann jedoch nur unter folgenden Bedingungen durchgeführt werden: 1. mit einer hohen räumlichen und zeitlichen Auflösung, 2. mit speziellen Kathetersystemen für eine intravaskuläre oder intramyokardiale Therapie und 3. mit einem wirksamen Medikament. Diese Übersichtsarbeit berichtet über die aktuellen Aspekte der iMR, nennt Beispiele in Bezug auf kardiale Interven tionen und stellt die Herausforderungen in Bezug auf die Zukunft der iMR dar. Interventional cardiovascular magnetic resonance (iCMR) makes new minimally invasive therapies possible and is an attractive alternative option with high soft-tissue contrast and the possibility of a three-dimensional MR angiography compared to conventional angiography-guided interventions. Interventional MR-navigated cardiovascular therapies represent a new discipline whose systematic development will foster minimally invasive interventional procedures without radiation exposure. MR-compatible endovascular catheters and guide wires are needed for delivery of devices and therapies. Catheter tracking is based on active and passive approaches. Currently performed MR-guided cardiovascular procedures have been used to monitor, navigate and track endovascular catheters and to deliver local therapies to the targets. Heating of endovascular MR catheters, guide wires and devices during imaging still presents high safety risks. Cardiovascular MR contrast media improve the capability of MRI by enhancing blood signal, pathologic targets (such as myocardial infarctions and atherosclerotic plaques) and tracking injected therapies (such as cells or genes). Labeling injected therapies or cells with MR contrast media leads interventionalists to trace the distribution, differentiation and survival. The requirements for this iCMR technique are (1) high spatial and temporal resolution imaging, (2) special catheters and devices, and (3) effective therapeutic drugs. This review summarizes current aspects of iCMR, provides examples of its use in the heart and beyond, discusses the infrastructure required for successful implementation of iCMR approaches, and outlines the challenges that must be overcome for iCMR to advance further.
    Herz 07/2008; 33(5):323-333. DOI:10.1007/s00059-008-3104-6 · 0.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, stem cell research has led to a better understanding of developmental biology, various diseases and its potential impact on regenerative medicine. A non-invasive method to monitor the transplanted stem cells repeatedly in vivo would greatly enhance our ability to understand the mechanisms that control stem cell death and identify trophic factors and signaling pathways that improve stem cell engraftment. MR imaging has been proven to be an effective tool for the in vivo depiction of stem cells with near microscopic anatomical resolution. In order to detect stem cells with MR, the cells have to be labeled with cell specific MR contrast agents. For this purpose, iron oxide nanoparticles, such as superparamagnetic iron oxide particles (SPIO), are applied, because of their high sensitivity for cell detection and their excellent biocompatibility. SPIO particles are composed of an iron oxide core and a dextran, carboxydextran or starch coat, and function by creating local field inhomogeneities, that cause a decreased signal on T2-weighted MR images. This presentation will demonstrate techniques for labeling of stem cells with clinically applicable MR contrast agents for subsequent non-invasive in vivo tracking of the labeled cells with MR imaging.
    Journal of Visualized Experiments 02/2008; DOI:10.3791/685
Show more