title: Cancer treatment using an optically inert Rose Bengal derivative combined with pulsed focused ultrasound.
abstract: Pulsed high intensity focused ultrasound (HIFU) has been combined with a photo-insensitive Rose Bengal derivative (RB2) to provide a synergistic cytotoxicity requiring the presence of both ultrasonic cavitation and drug. In vitro tests have shown that a short treatment (less than 30 s) of pulsed HIFU with peak negative pressure >7 MPa (~27 W acoustic power at 1.4 MHz) destroys >95% of breast cancer cells MDA-MB-231 in suspension with >10 μM of the compound. Neither the pulsed HIFU nor the RB2 compound was found to have any significant impact on the viability of the cells when used alone. Introducing an antioxidant (N-acetylcysteine) reduced the effectiveness of the treatment. In vivo tests using these same cells growing as a xenograft in nu/nu mice were also done. An ultrasound contrast agent (Optison) and lower frequency (1.0 MHz) was used to help initiate cavitation at the tumor site. We were able to demonstrate tumor regression with cavitation alone, however, addition of RB2 compound injected i.v. yielded a substantial synergistic improvement.
authors.affiliation: Department of Radiology, The Methodist Hospital Research Institute, Weill Medical College of Cornell University, 6565 Fannin St., Houston, TX 77030, USA.
authors.forename: Yoo-Shin
authors.initials: YS
authors.lastname: Kim
authors.forename: Valentina
authors.initials: V
authors.lastname: Rubio
authors.forename: Jianjun
authors.initials: J
authors.lastname: Qi
authors.forename: Rongmin
authors.initials: R
authors.lastname: Xia
authors.forename: Zheng-Zheng
authors.initials: ZZ
authors.lastname: Shi
authors.forename: Leif
authors.initials: L
authors.lastname: Peterson
authors.forename: Ching-Hsuan
authors.initials: CH
authors.lastname: Tung
authors.forename: Brian E
authors.initials: BE
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012395:Rose Bengal / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D012395:Rose Bengal