Investigations into thermally mediated drug delivery using a preclinical system for MRI-guided focused ultrasound

Robert Staruch, Rajiv Chopra, Kullervo Hynynen

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

1 Scopus citations

Abstract

The objective of this research was to investigate the use of a preclinical system for MRI-guided focused ultrasound to achieve MRI-controlled hyperthermia and thermally-mediated drug delivery in vivo. Here we report results from ten rabbits, where a focused xultrasound (FUS) beam was scanned in a circular trajectory to heat 10-15 mm diameter regions in normal thigh to 43°C for 20-30 minutes. MRI thermometry was used for closed-loop feedback control to achieve temporally and spatially uniform heating. Lyso-thermosensitive pegylated liposomal doxorubicin (ThermoDox®, Celsion Corporation, Columbia, MD) was infused intravenously during hyperthermia, and the tissue doxorubicin concentration was measured by the fluorescence intensity of homogenized tissue samples from heated and unheated thigh, obtained 2 hours after heating. Closed-loop control of FUS hyperthermia using MRI thermometry achieved temperature distributions with mean, T90 and T10 of 42.9°C, 41.0°C and 44.8°C across the 10 mm diameter target, varying ±0.9°C (SD) over 20 min. Drug concentrations in heated regions were, on average 15.3 ± 8.1 (SD) times higher than in the unheated contralateral thigh. The results show the feasibility of using MRI-controlled FUS hyperthermia for preclinical studies of thermally mediated drug delivery with temperature-sensitive liposomes.

Original languageEnglish (US)
Title of host publication10th International Symposium on Therapeutic Ultrasound, ISTU 2010
Pages163-167
Number of pages5
DOIs
StatePublished - Oct 13 2011
Event10th International Symposium on Therapeutic Ultrasound, ISTU 2010 - Tokyo, Japan
Duration: Jun 9 2010Jun 12 2010

Publication series

NameAIP Conference Proceedings
Volume1359
ISSN (Print)0094-243X
ISSN (Electronic)1551-7616

Other

Other10th International Symposium on Therapeutic Ultrasound, ISTU 2010
CountryJapan
CityTokyo
Period6/9/106/12/10

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Keywords

  • Focused ultrasound
  • Liposomes
  • MRI thermometry
  • Targeted drug delivery

ASJC Scopus subject areas

  • Physics and Astronomy(all)

Cite this

Staruch, R., Chopra, R., & Hynynen, K. (2011). Investigations into thermally mediated drug delivery using a preclinical system for MRI-guided focused ultrasound. In 10th International Symposium on Therapeutic Ultrasound, ISTU 2010 (pp. 163-167). (AIP Conference Proceedings; Vol. 1359). https://doi.org/10.1063/1.3607899