PURPOSE: 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. PROCEDURES: 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.
PURPOSE: 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. PROCEDURES: The humanglioblastoma 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: Yawei Qiao; Margaret R Spitz; Zhaozheng Guo; Mohammad Hadeyati; Lawrence Grossman; Kenneth H Kraemer; Qingyi Wei Journal: Mutat Res Date: 2002-11-30 Impact factor: 2.433
Authors: Nathan C Shaner; Robert E Campbell; Paul A Steinbach; Ben N G Giepmans; Amy E Palmer; Roger Y Tsien Journal: Nat Biotechnol Date: 2004-11-21 Impact factor: 54.908
Authors: Barjor Gimi; Noriko Mori; Ellen Ackerstaff; Emma E Frost; Jeff W M Bulte; Zaver M Bhujwalla Journal: Neoplasia Date: 2006-03 Impact factor: 5.715
Authors: Tatsuya Abe; Hiroaki Wakimoto; Robert Bookstein; Daniel C Maneval; E Antonio Chiocca; James P Basilion Journal: Cancer Gene Ther Date: 2002-03 Impact factor: 5.987
Authors: R Nishikawa; X D Ji; R C Harmon; C S Lazar; G N Gill; W K Cavenee; H J Huang Journal: Proc Natl Acad Sci U S A Date: 1994-08-02 Impact factor: 11.205