title: Ultrasound-mediated microbubble enhancement of radiation therapy studied using three-dimensional high-frequency power Doppler ultrasound.
abstract: Tumor responses to high-dose (>8 Gy) radiation therapy are tightly connected to endothelial cell death. In the study described here, we investigated whether ultrasound-activated microbubbles can locally enhance tumor response to radiation treatments of 2 and 8 Gy by mechanically perturbing the endothelial lining of tumors. We evaluated vascular changes resulting from combined microbubble and radiation treatments using high-frequency 3-D power Doppler ultrasound in a breast cancer xenograft model. We compared treatment effects and monitored vasculature damage 3 hours, 24 hours and 7 days after treatment delivery. Mice treated with 2 Gy radiation and ultrasound-activated microbubbles exhibited a decrease in vascular index to 48 ± 10% at 24 hours, whereas vascular indices of mice treated with 2 Gy radiation alone or microbubbles alone were relatively unchanged at 95 ± 14% and 78 ± 14%, respectively. These results suggest that ultrasound-activated microbubbles enhance the effects of 2 Gy radiation through a synergistic mechanism, resulting in alterations of tumor blood flow. This novel therapy may potentiate lower radiation doses to preferentially target endothelial cells, thus reducing effects on neighboring normal tissue and increasing the efficacy of cancer treatments.
authors.affiliation: Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sheldon J J
authors.initials: SJ
authors.lastname: Kwok
authors.forename: Ahmed
authors.initials: A
authors.lastname: El Kaffas
authors.forename: Priscilla
authors.initials: P
authors.lastname: Lai
authors.forename: Azza
authors.initials: A
authors.lastname: Al Mahrouki
authors.forename: Justin
authors.initials: J
authors.lastname: Lee
authors.forename: Sara
authors.initials: S
authors.lastname: Iradji
authors.forename: William Tyler
authors.initials: WT
authors.lastname: Tran
authors.forename: Anoja
authors.initials: A
authors.lastname: Giles
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Czarnota
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003287:Contrast Media / Q000627:therapeutic use; D005466:Fluorocarbons / Q000627:therapeutic use*; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles / Q000627:therapeutic use; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; C042852:perflutren
keywords: High-frequency ultrasound; Microbubble perturbation; Power Doppler ultrasound; Radiation therapy; Radiotherapy; Tumor vascular imaging; Tumor vasculature; Ultrasound-activated microbubbles; Vascular disrupting agents