title: In vitro validation of bioluminescent monitoring of disease progression and therapeutic response in leukaemia model animals.
abstract: OBJECTIVE
  The application of in vivo bioluminescence imaging to non-invasive, quantitative monitoring of tumour models relies on a positive correlation between the intensity of bioluminescence and the tumour burden. We conducted cell culture studies to investigate the relationship between bioluminescent signal intensity and viable cell numbers in murine leukaemia model cells.
  
  
  METHODS
  Interleukin-3 (IL-3)-dependent murine pro-B cell line Ba/F3 was transduced with firefly luciferase to generate cells expressing luciferase stably under the control of a retroviral long terminal repeat. The luciferase-expressing cells were transduced with p190 BCR-ABL to give factor-independent proliferation. The cells were cultured under various conditions, and bioluminescent signal intensity was compared with viable cell numbers and the cell cycle stage.
  
  
  RESULTS
  The Ba/F3 cells showed autonomous growth as well as stable luciferase expression following transduction with both luciferase and p190 BCR-ABL, and in vivo bioluminescence imaging permitted external detection of these cells implanted into mice. The bioluminescence intensities tended to reflect cell proliferation and responses to imatinib in cell culture studies. However, the luminescence per viable cell was influenced by the IL-3 concentration in factor-dependent cells and by the stage of proliferation and imatinib concentration in factor-independent cells, thereby impairing the proportionality between viable cell number and bioluminescent signal intensity. Luminescence per cell tended to vary in association with the fraction of proliferating cells.
  
  
  CONCLUSIONS
  Although in vivo bioluminescence imaging would allow non-invasive monitoring of leukaemia model animals, environmental factors and therapeutic interventions may cause some discrepancies between tumour burden and bioluminescence intensity.
authors.affiliation: Department of Radiology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. inoueys-tky@umin.ac.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Inoue
authors.forename: Arinobu
authors.initials: A
authors.lastname: Tojo
authors.forename: Rieko
authors.initials: R
authors.lastname: Sekine
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Soda
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Akiko
authors.initials: A
authors.lastname: Nomura
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Izawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Okubo
authors.forename: Kuni
authors.initials: K
authors.lastname: Ohtomo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004195:Disease Models, Animal; D018450:Disease Progression; D007938:Leukemia / Q000175:diagnosis* / Q000628:therapy*; D008156:Luciferases; D008163:Luminescent Measurements / Q000379:methods*; D008164:Luminescent Proteins; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods*; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D008164:Luminescent Proteins; D008156:Luciferases