Tumor radiation response enhancement by acoustical stimulation of the vasculature.
We have discovered that ultrasound-mediated microbubble vascular disruption can enhance tumor responses to radiation in vivo. We demonstrate this effect using a human PC3 prostate cancer xenograft model. Results indicate a synergistic effect in vivo with combined single treatments of ultrasound-stimulated microbubble vascular perturbation and radiation inducing an over 10-fold greater cell kill with combined treatments. We further demonstrate with experiments in vivo that induction of ceramide-related endothelial cell apoptosis, leading to vascular disruption, is a causative mechanism. In vivo experiments with ultrasound and bubbles permit radiation doses to be decreased significantly for comparable effect. We envisage this unique combined ultrasound-based vascular perturbation and radiation treatment method being used to enhance the effects of radiation in a tumor, leading to greater tumor eradication.
Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. Gregory.Czarnota@sunnybrook.ca
Gregory J
GJ
Czarnota
Raffi
R
Karshafian
Peter N
PN
Burns
Shun
S
Wong
Azza
A
Al Mahrouki
Justin W
JW
Lee
Amanda
A
Caissie
William
W
Tran
Christina
C
Kim
Melissa
M
Furukawa
Emily
E
Wong
Anoja
A
Giles
D000161:Acoustic Stimulation / Q000379:methods*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism; D003131:Combined Modality Therapy / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D004730:Endothelium, Vascular / Q000166:cytology* / Q000528:radiation effects; D006652:Histological Techniques; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D045423:Microbubbles / Q000627:therapeutic use*; D008856:Microscopy, Fluorescence; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D014183:Transplantation, Heterologous; D014463:Ultrasonography
D002518:Ceramides; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine