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Responses of Medulloblastoma Cells to Radiation Dosimetric Parameters in Intensity-Modulated Radiation Therapy

J Park

J Park1,2,3,4*, J Park5 , S Rogalla1,2,3 , D Woo6 , D Lee4,6 , H Park7 , C Contag1,2,3 , T Suh4,8 (1) Dept. of Pediatrics, Stanford University School of Medicine, Stanford, CA (2) Molecular Imaging Program at Stanford, Stanford, CA (3) Bio-X Program, Stanford, CA (4) Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul, Korea (5) Proton Therapy Center, National Cancer Center, Goyang, Korea (6) Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea (7) Dept. of Radiation Oncology, Ajou University School of Medicine, Suwon, Korea (8) Dept. of Biomedical Engineering, The Catholic University of Korea, Seoul, Korea


SU-E-J-274 (Sunday, July 12, 2015) 3:00 PM - 6:00 PM Room: Exhibit Hall

Purpose: To evaluate radiation responses of the medulloblastoma cell line Daoy in intensity-modulated radiation therapy (IMRT), quantitative variations to variable radiation dosimetic parameters were tracked by bioluminescent images (BLIs).
Methods: The luciferase and green fluorescent protein positive Daoy cells were cultured on dishes. The medulloblastoma cells irradiated to different dose rate, interval of fractionated doses, field margin and misalignment, and dose uniformity in IMRT were monitored using bioluminescent images. The cultured cells were placed into a dedicated acrylic phantom to deliver intensity-modulated fluences and calculate accurate predicted dose distribution. The radiation with dose rate from 0.5 Gy/min to 15 Gy/min was irradiated by adjusting monitor unit per minute and source-to-surface distances. The intervals of fractionated dose delivery were changed considering the repair time of double strand breaks (DSB) revealed by straining of gamma-H2AX.The effect of non-uniform doses on the cells were visualized by registering dose distributions and BLIs. The viability according to dosimetric parameters was correlated with bioluminescent intensities for cross-check of radiation responses.
Results: The DSB and cell responses due to the first fractionated dose delivery significantly affected final tumor control rather than other parameters. The missing tumor volumes due to the smaller field margin than the tumor periphery or field misalignment caused relapse of cell responses on BLIs. The dose rate and gradient had effect on initial responses but could not bring out the distinguishable killing effect on cancer cells.
Conclusion: Visualized and quantified bioluminescent images were useful to correlate the dose distributions with spatial radiation effects on cells. This would derive the effective combination of dose delivery parameters and fractionation. Radiation responses in particular IMRT configuration could be reflected to image based-dose re-optimization.

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