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 publicationAIP Conference Proceedings
Pages362-367
Number of pages6
Volume1481
DOIs
StatePublished - 2012
Event11th International Symposium on Therapeutic Ultrasound, ISTU 2011 - New York, NY, United States
Duration: Apr 11 2011Apr 13 2011

Other

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

Fingerprint

hyperthermia
delivery
drugs
bones
rabbits
tumors
heating
muscles
thigh
bone marrow
transducers
trajectories
fluorescence
temperature

Keywords

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

ASJC Scopus subject areas

  • Physics and Astronomy(all)

Cite this

Investigations into the use of MRI-controlled focused ultrasound for hyperthermia-mediated drug delivery. / Staruch, Robert; Chopra, Rajiv; Hynynen, Kullervo.

AIP Conference Proceedings. Vol. 1481 2012. p. 362-367.

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

Staruch, R, Chopra, R & Hynynen, K 2012, Investigations into the use of MRI-controlled focused ultrasound for hyperthermia-mediated drug delivery. in AIP Conference Proceedings. vol. 1481, pp. 362-367, 11th International Symposium on Therapeutic Ultrasound, ISTU 2011, New York, NY, United States, 4/11/11. https://doi.org/10.1063/1.4757362
Staruch, Robert ; Chopra, Rajiv ; Hynynen, Kullervo. / Investigations into the use of MRI-controlled focused ultrasound for hyperthermia-mediated drug delivery. AIP Conference Proceedings. Vol. 1481 2012. pp. 362-367
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