The Society for Thermal Medicine met in Tucson in early April, 2009. There were numerous presentations of interest to those of us in Focused Ultrasound Surgery. On Saturday afternoon, April 4, there was a symposium devoted entirely to MRgFUS (Symposium III: New Developments in MR-Guided High Intensity Focused Ultrasound).
Presentations included:
“MRI-guided focused ultrasound for the treatment of brain and prostate cancer”
By Nathan McDannold , Brigham and Women’s Hospital, Boston, MA, United States.
Initial clinical treatments in three patients with glioblastoma demonstrate that the device (Exablate 3000, Insightec, Inc.) is capable of focusing through the skull. The prostate system consists of a 1000-element transrectal focused ultrasound probe. In preclinical s in dogs at the Brigham, the focal heating was readily observed with proton resonance frequency (PRF) MR temperature imaging, contrast enhanced MRI and histology. Prostate gland motion during their experiments suggested a need for motion tracking.
“MR Guided High Intensity Focused Ultrasound For Treatment of Bone Metastases”
By Mark Hurwitz , Dana-Farber/Brigham & Women’s Cancer Center, Boston, MA, United States.
Bone metastases are a common clinical problem encountered in oncology. For many patients with metastatic disease,
painful bone metastases often have a major impact on quality of life. An international definitive phase III trial is now open to patient accrual.
“Next Generation Techniques in MR-HIFU: Volumetric Heating with Thermal Feedback”
By Sham Sokka, Phillips Inc., Andover, MA, United States.
MR-HIFU volumetric heating with closed loop thermal feedback and multi-slice MR temperature imaging allows for more rapid treatment. Volumetric heating is performed by high-speed scanning of the HIFU focal point over volumes 8-16 times that of conventional MR-HIFU exposure. During these sonications, heat deposition is controlled with closed–loop feedback algorithms that monitor the MR real-time temperature maps and adjust the duration and location of the focused ultrasound exposure to achieve the desired temperature or thermal dose in the volume.
“A Small-Animal MRI-guided Mechanically-Scanned Focused Ultrasound System for Hyperthermia Mediated Drug Delivery”
Robert Staruch, Rajiv Chopra, Kullervo Hynynen, Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. The use of long-circulating temperature-sensitive drug carriers provides a mechanism for locally triggering the rapid release of high concentrations of active drug in the tumor, with reduced systemic toxicity. Use of MRgFUS ablation systems to maintain hyperthermic temperatures for localized drug delivery requires closed-loop feedback control based on MR temperature images, and must be robust to hyperthermia-induced changes in perfusion.
The MRgFUS Symposium was immediately followed by another symposium with several presentations relevant to FUS (Symposium IV: Nano-Technology and Thermal Medicine):
“Combining temperature sensitive liposomes with radiofrequency ablation and high intensity focused ultrasound”
Matthew Dreher, National Institutes of Health, Bethesda, MD, United States
Temperature sensitive liposomes for enhanced drug delivery to solid tumors have been investigated for three decades with impressive accomplishments in preclinical models but only recently has clinical adoption of the technology become reality and gained momentum. The ive of this study was to combine lysolipid-containing temperature sensitive liposomes (LTSLs) with clinical image-guided hyperthermia devices such as radiofrequency ablation (RFA) or high intensity focused ultrasound (HIFU). HIFU is most often studied for ablating tissue, but it can also be used in a pulsed mode that results in small temperature elevations in the range of 40-42ºC (2min), which is optimal for combination with LTSLs.
“Thermosensitive liposomes: effect of heat-triggered fast release on drug delivery and tumor vasculature”
Ashley Manzoor, Ji-Young Park, David Needham, Mark W. Dewhirst, Duke University, Durham, NC, United States
They developed a low temperature-sensitive liposome loaded with doxorubicin (Dox-LTSL) that releases large amounts of drug within 20 seconds of reaching its transition temperature. This formulation has shown dramatic anti-tumor effects, delivering up to 30 times more drug to the tumor than free doxorubicin. Dox delivered with LTSLs exhibits an extended period of increasing accumulation and efflux delay, increasing the time the tumor is exposed to maximum drug levels. This work demonstrates the ability of heat-triggered release from liposomes to improve drug delivery kinetics and influence uptake of nearby endothelial cells.
“Long-circulating thermosensitive liposomes for drug delivery to solid tumors – a two step approach.”
Gerben A. Koning, Li Li, Debby Schipper, Tom Wijnberg, Gerard C. van Rhoon, Lars H. Lindner, Alexander M.M. Eggermont, Timo L.M. ten Hagen, Erasmus MC,
Department of Surgical Oncology, Laboratory Experimental Surgical Oncology,
Rotterdam, Netherlands, Erasmus MC, Department Radiotherapy, Unit Hyperthermia, Rotterdam, Netherlands.
Bioavailability is dependent on release of the drug from the carrier and subsequent passage of the tumor cell membrane. 1.) Mild hyperthermia (<41 °C) is applied to further increase levels of liposome extravasation, and 2.) A slightly higher temperature (~42 °C) is used to trigger the release of the content of the liposomes. Optimally formulated liposomes were stable up to 40 °C and started to release their contents above 41°C, both in vitro and in vivo. The release process in vivo was clearly visualized by intravital confocal microscopy in the dorsal skin-fold window chamber.
There were numerous other presentations relevant to MRgFUS throughout the meeting, some of which will be reported shortly. MRgFUS is emerging as an optimal technique for precise delivery of thermal energy, so that much of the work presented that was not directly linked to MRgFUS will merge into the MRgFUS realm in the future. This annual meeting is very relevant to the interests and goals of the FUSF.
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