Bioluminescent evaluation of the therapeutic effects of total body irradiation in a murine hematological malignancy model

Inoue, Yusuke; Izawa, Kiyoko; Kiryu, Shigeru; Kobayashi, Seiichiro; Tojo, Arinobu; Ohtomo, Kuni

doi:10.1016/j.exphem.2008.08.004

« Previous Next »Experimental Hematology
Volume 36, Issue 12 , Pages 1634-1641, December 2008

Bioluminescent evaluation of the therapeutic effects of total body irradiation in a murine hematological malignancy model

Yusuke Inoue
- Department of Radiology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- Offprint requests to: Yusuke Inoue, MD, Department of Radiology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Kiyoko Izawa
- Division of Molecular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Shigeru Kiryu
- Department of Radiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Seiichiro Kobayashi
- Division of Molecular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Arinobu Tojo
- Division of Molecular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Kuni Ohtomo
- Department of Radiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Received 28 June 2008; received in revised form 18 August 2008; accepted 20 August 2008. published online 27 October 2008.

Objective

We investigated the utility of in vivo bioluminescence imaging (BLI) in assessing the therapeutic effects of total body irradiation (TBI) in a murine hematological malignancy model.

Materials and Methods

The suspension of Ba/F3 cells transduced with firefly luciferase and p190 BCR-ABL genes was exposed to ionizing radiation, and viable cell numbers and bioluminescent signals were measured serially. Mice intravenously inoculated with the cells underwent TBI at various doses. In vivo BLI was performed repeatedly until spontaneous death, and whole-body bioluminescence signals were determined as an indicator of whole-body tumor burden.

Results

In the cell culture study, bioluminescence signals generally reflected viable cell numbers, despite some overestimation immediately after irradiation. Sublethal TBI in mice transiently depressed the increase in whole-body signals and prolonged survival. Spontaneous death occurred at similar signal levels regardless of radiation dose. A significant negative correlation was found between survival and whole-body signal early after TBI. Significant dose dependence was demonstrated for both survival and signal increase early after TBI and was more evident for signal increase. Lethally irradiated mice without bone marrow transplantation died while showing weak signals. In mice receiving lethal TBI and syngeneic bone marrow transplantation, signal reduction and prolongation of survival were prominent, and whole-body signals at death were similar to those in nonirradiated or sublethally irradiated mice.

Conclusion

In vivo BLI allows longitudinal, quantitative evaluation of the response to TBI in mice of a hematological malignancy model. Antitumor effects can be assessed early and reliably using in vivo BLI.