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In vitro validation of bioluminescent monitoring of disease progression and therapeutic response in leukaemia model animals

  • Yusuke InoueEmail author
  • Arinobu Tojo
  • Rieko Sekine
  • Yasushi Soda
  • Seiichiro Kobayashi
  • Akiko Nomura
  • Kiyoko Izawa
  • Toshio Kitamura
  • Toshiyuki Okubo
  • Kuni Ohtomo
Molecular imaging

Abstract

Purpose

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.

Conclusion

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.

Keywords

Luciferase Leukaemia Retroviruses Imatinib mesylate Cell cycle 

Notes

Acknowledgements

This work was supported, in part, by grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Yusuke Inoue
    • 1
    Email author
  • Arinobu Tojo
    • 2
  • Rieko Sekine
    • 2
  • Yasushi Soda
    • 2
  • Seiichiro Kobayashi
    • 2
  • Akiko Nomura
    • 2
  • Kiyoko Izawa
    • 2
  • Toshio Kitamura
    • 3
  • Toshiyuki Okubo
    • 1
  • Kuni Ohtomo
    • 4
  1. 1.Department of Radiology, Institute of Medical ScienceUniversity of TokyoTokyoJapan
  2. 2.Division of Molecular Therapy, Advanced Clinical Research CentreUniversity of TokyoTokyoJapan
  3. 3.Division of Cellular Therapy, Advanced Clinical Research CentreUniversity of TokyoTokyoJapan
  4. 4.Department of Radiology, Graduate School of MedicineUniversity of TokyoTokyoJapan

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