title: In Vitro Investigation of the Individual Contributions of Ultrasound-Induced Stable and Inertial Cavitation in Targeted Drug Delivery.
abstract: Ultrasound-mediated targeted drug delivery is a therapeutic modality under development with the potential to treat cancer. Its ability to produce local hyperthermia and cell poration through cavitation non-invasively makes it a candidate to trigger drug delivery. Hyperthermia offers greater potential for control, particularly with magnetic resonance imaging temperature measurement. However, cavitation may offer reduced treatment times, with real-time measurement of ultrasonic spectra indicating drug dose and treatment success. Here, a clinical magnetic resonance imaging-guided focused ultrasound surgery system was used to study ultrasound-mediated targeted drug delivery in vitro. Drug uptake into breast cancer cells in the vicinity of ultrasound contrast agent was correlated with occurrence and quantity of stable and inertial cavitation, classified according to subharmonic spectra. During stable cavitation, intracellular drug uptake increased by a factor up to 3.2 compared with the control. Reported here are the value of cavitation monitoring with a clinical system and its subsequent employment for dose optimization.
authors.affiliation: Institute for Medical Science and Technology, School of Medicine, University of Dundee, Dundee, United Kingdom; Capsutech Ltd., Nazareth, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Gourevich
authors.affiliation: Institute for Medical Science and Technology, School of Medicine, University of Dundee, Dundee, United Kingdom; InSightec Ltd., Haifa, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Volovick
authors.affiliation: Institute for Medical Science and Technology, School of Medicine, University of Dundee, Dundee, United Kingdom; InSightec Ltd., Haifa, Israel.
authors.forename: Osnat
authors.initials: O
authors.lastname: Dogadkin
authors.affiliation: Institute for Medical Science and Technology, School of Medicine, University of Dundee, Dundee, United Kingdom.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Engineering, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Mulvana
authors.affiliation: Department of Biomedical Engineering, Technion, Haifa, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Medan
authors.affiliation: Institute for Medical Science and Technology, School of Medicine, University of Dundee, Dundee, United Kingdom.
authors.forename: Andreas
authors.initials: A
authors.lastname: Melzer
authors.affiliation: Institute for Medical Science and Technology, School of Medicine, University of Dundee, Dundee, United Kingdom. Electronic address: s.cochran@dundee.ac.uk.
authors.forename: Sandy
authors.initials: S
authors.lastname: Cochran
mesh_terms: D002463:Cell Membrane Permeability / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects*; D004307:Dose-Response Relationship, Radiation; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018274:Electroporation / Q000379:methods*; D061986:MCF-7 Cells; D011829:Radiation Dosage; D013010:Sonication / Q000379:methods*; D000069453:Ultrasonic Waves
chemical_list: D004317:Doxorubicin
keywords: Cancer cell; Cavitation; Focused ultrasound; Microbubbles; Subharmonic; Targeted drug delivery; Ultrasound contrast agent