title: Development of a three-dimensional in vitro model for longitudinal observation of cell behavior: monitoring by magnetic resonance imaging and optical imaging.
abstract: OBJECTIVE
  The aim of this study is the development of a three-dimensional multicellular spheroid cell culture model for the longitudinal comparative and large-scale screening of cancer cell proliferation with noninvasive molecular imaging techniques under controlled and quantifiable conditions.
  
  
  METHODS
  The human glioblastoma cell line Gli36DeltaEGFR was genetically modified to constitutively express the fluorescence protein mCherry, and additionally labeled with iron oxide nanoparticles for high-field MRI detection. The proliferation of aggregates was longitudinally monitored with fluorescence imaging and correlated with aggregate size by light microscopy, while MRI measurements served localization in 3D space. Irradiation with gamma-rays was used to detect proliferational response.
  
  
  RESULTS
  Cell proliferation in the stationary three-dimensional model can be observed over days with high accuracy. A linear relationship of fluorescence intensity with cell aggregate size was found, allowing absolute quantitation of cells in a wide range of cell amounts. Glioblastoma cells showed pronounced suppression of proliferation for several days following high-dose gamma-irradiation.
  
  
  CONCLUSIONS
  Through the combination of two-dimensional optical imaging and 3D MRI, the position of individual cell aggregates and their corresponding light emission can be detected. This allows an exact quantification of cell proliferation, with a focus on very small cell amounts (below 100 cells) using high resolution noninvasive techniques as a well-controlled basis for further cell transplantation studies.
authors: In-vivo-NMR-Laboratory, Max-Planck-Institute for Neurological Research, Gleuelerstrasse 50, 50931 Cologne, Germany.
authors: Klaus
authors: K
authors: Kruttwig
authors: Chantal
authors: C
authors: Brueggemann
authors: Eric
authors: E
authors: Kaijzel
authors: Susanne
authors: S
authors: Vorhagen
authors: Thomas
authors: T
authors: Hilger
authors: Clemens
authors: C
authors: Löwik
authors: Mathias
authors: M
authors: Hoehn
mesh_terms: D002449:Cell Aggregation; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003911:Dextrans; D052203:Ferrosoferric Oxide / Q000378:metabolism; D005453:Fluorescence; D005720:Gamma Rays; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008954:Models, Biological; D057054:Molecular Imaging / Q000379:methods*; D055620:Optical Phenomena; D013194:Staining and Labeling
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides; D052203:Ferrosoferric Oxide