Microbubble and ultrasound radioenhancement of bladder cancer.
BACKGROUND
Tumour vasculature is an important component of tumour growth and survival. Recent evidence indicates tumour vasculature also has an important role in tumour radiation response. In this study, we investigated ultrasound and microbubbles to enhance the effects of radiation.


METHODS
Human bladder cancer HT-1376 xenografts in severe combined immuno-deficient mice were used. Treatments consisted of no, low and high concentrations of microbubbles and radiation doses of 0, 2 and 8 Gy in short-term and longitudinal studies. Acute response was assessed 24 h after treatment and longitudinal studies monitored tumour response weekly up to 28 days using power Doppler ultrasound imaging for a total of 9 conditions (n=90 animals).


RESULTS
Quantitative analysis of ultrasound data revealed reduced blood flow with ultrasound-microbubble treatments alone and further when combined with radiation. Tumours treated with microbubbles and radiation revealed enhanced cell death, vascular normalisation and areas of fibrosis. Longitudinal data demonstrated a reduced normalised vascular index and increased tumour cell death in both low and high microbubble concentrations with radiation.


CONCLUSIONS
Our study demonstrated that ultrasound-mediated microbubble exposure can enhance radiation effects in tumours, and can lead to enhanced tumour cell death.
Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
W T
WT
Tran
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S
Iradji
E
E
Sofroni
A
A
Giles
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D
Eddy
G J
GJ
Czarnota
D000818:Animals; D016923:Cell Death / Q000528:radiation effects; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000528:radiation effects; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D016513:Mice, SCID; D045423:Microbubbles; D009389:Neovascularization, Pathologic / Q000532:radiotherapy; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000528:radiation effects; D014465:Ultrasonics; D014463:Ultrasonography; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D023041:Xenograft Model Antitumor Assays
D003287:Contrast Media; D011838:Radiation-Sensitizing Agents