Investigations into the use of MRI-controlled focused ultrasound for hyperthermia-mediated drug delivery

Robert Staruch, Rajiv Chopra, Kullervo Hynynen

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Combining localized heating with thermosensitive liposomes provides a means for triggering the rapid release of active drug in a targeted region. The objective of this research was to demonstrate the feasibility of using MRI-controlled focused ultrasound hyperthermia in rabbit VX2 tumors and bone to achieve thermally-mediated localized drug delivery. To generate a uniform region of mild heating, a focused ultrasound transducer was mechanically scanned in a circular trajectory by an MRI-compatible positioner. MRI temperature images were continuously acquired during scanned heating, and applied power was adjusted in a multi-point feedbackcontrol loop based on temperatures measured in tumors or in soft tissue adjacent to bone. Lysothermosensitive liposomal doxorubicin was infused intravenously during hyperthermia. Two hours post-treatment, unabsorbed liposomes were flushed from the vasculature with saline. Drug concentrations in homogenized tissues sampled from heated and unheated regions were measured by doxorubicin fluorescence. MRI-controlled focused ultrasound achieved stable heating at 43°C for 20 minutes in VX2 tumors implanted in the thighs of 5 rabbits, and at the muscle-bone interface of 9 rabbits. Localized heating resulted in a 20-fold increase in doxorubicin concentration localized to heated tumors, with 8 and 17-fold increases in bone marrow and muscle adjacent to the heated bone interface.

Original languageEnglish (US)
Title of host publication11th International Symposium on Therapeutic Ultrasound
Pages362-367
Number of pages6
DOIs
StatePublished - Dec 1 2012
Event11th International Symposium on Therapeutic Ultrasound, ISTU 2011 - New York, NY, United States
Duration: Apr 11 2011Apr 13 2011

Publication series

NameAIP Conference Proceedings
Volume1481
ISSN (Print)0094-243X
ISSN (Electronic)1551-7616

Other

Other11th International Symposium on Therapeutic Ultrasound, ISTU 2011
CountryUnited States
CityNew York, NY
Period4/11/114/13/11

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Keywords

  • MRI thermometry
  • focused ultrasound
  • liposomes
  • targeted drug delivery

ASJC Scopus subject areas

  • Physics and Astronomy(all)

Cite this

Staruch, R., Chopra, R., & Hynynen, K. (2012). Investigations into the use of MRI-controlled focused ultrasound for hyperthermia-mediated drug delivery. In 11th International Symposium on Therapeutic Ultrasound (pp. 362-367). (AIP Conference Proceedings; Vol. 1481). https://doi.org/10.1063/1.4757362