TY - JOUR
T1 - Localised drug release using MRI-controlled focused ultrasound hyperthermia
AU - Staruch, Robert
AU - Chopra, Rajiv
AU - Hynynen, Kullervo
N1 - Funding Information:
Declaration of interest: Kullervo Hynynen and Rajiv Chopra are founders and have shares in FUS Instruments, a company that is commercialising the preclinical FUS system described in these experiments. Thermosensitive liposomes were provided by Celsion. This work is supported by funding through a Terry Fox Foundation New Frontiers Program project grant from the National Cancer Institute of Canada, and by an Ontario Research Fund grant from the Government of Ontario, Canada. The authors alone are responsible for the content and writing of the paper.
PY - 2011/3
Y1 - 2011/3
N2 - Purpose: Thermosensitive liposomes provide a mechanism for triggering the local release of anticancer drugs, but this technology requires precise temperature control in targeted regions with minimal heating of surrounding tissue. The objective of this study was to evaluate the feasibility of using MRI-controlled focused ultrasound (FUS) and thermosensitive liposomes to achieve thermally mediated localised drug delivery in vivo. Materials and methods: Results are reported from ten rabbits, where a FUS beam was scanned in a circular trajectory to heat 10-15 mm diameter regions in normal thigh to 43°C for 20-30 min. MRI thermometry was used for closed-loop feedback control to achieve temporally and spatially uniform heating. Lyso-thermosensitive liposomal doxorubicin was infused intravenously during hyperthermia. Unabsorbed liposomes were flushed from the vasculature by saline perfusion 2 h later, and tissue samples were harvested from heated and unheated thigh regions. The fluorescence intensity of the homogenised samples was used to calculate the concentration of doxorubicin in tissue. Results: Closed-loop control of FUS heating using MRI thermometry achieved temperature distributions with mean, T90 and T10 of 42.9°C, 41.0°C and 44.8°C, respectively, over a period of 20 min. Doxorubicin concentrations were significantly higher in tissues sampled from heated than unheated regions of normal thigh muscle (8.3 versus 0.5 ng/mg, mean per-animal difference = 7.8 ng/mg, P < 0.05, Wilcoxon matched pairs signed rank test). Conclusions: The results show the potential of MRI-controlled focused ultrasound hyperthermia for enhanced local drug delivery with temperature-sensitive drug carriers.
AB - Purpose: Thermosensitive liposomes provide a mechanism for triggering the local release of anticancer drugs, but this technology requires precise temperature control in targeted regions with minimal heating of surrounding tissue. The objective of this study was to evaluate the feasibility of using MRI-controlled focused ultrasound (FUS) and thermosensitive liposomes to achieve thermally mediated localised drug delivery in vivo. Materials and methods: Results are reported from ten rabbits, where a FUS beam was scanned in a circular trajectory to heat 10-15 mm diameter regions in normal thigh to 43°C for 20-30 min. MRI thermometry was used for closed-loop feedback control to achieve temporally and spatially uniform heating. Lyso-thermosensitive liposomal doxorubicin was infused intravenously during hyperthermia. Unabsorbed liposomes were flushed from the vasculature by saline perfusion 2 h later, and tissue samples were harvested from heated and unheated thigh regions. The fluorescence intensity of the homogenised samples was used to calculate the concentration of doxorubicin in tissue. Results: Closed-loop control of FUS heating using MRI thermometry achieved temperature distributions with mean, T90 and T10 of 42.9°C, 41.0°C and 44.8°C, respectively, over a period of 20 min. Doxorubicin concentrations were significantly higher in tissues sampled from heated than unheated regions of normal thigh muscle (8.3 versus 0.5 ng/mg, mean per-animal difference = 7.8 ng/mg, P < 0.05, Wilcoxon matched pairs signed rank test). Conclusions: The results show the potential of MRI-controlled focused ultrasound hyperthermia for enhanced local drug delivery with temperature-sensitive drug carriers.
KW - MRI thermometry
KW - feedback control
KW - heat targeted drug delivery
KW - high intensity focused ultrasound
KW - thermosensitive liposomes
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U2 - 10.3109/02656736.2010.518198
DO - 10.3109/02656736.2010.518198
M3 - Article
C2 - 21158487
AN - SCOPUS:79951642334
SN - 0265-6736
VL - 27
SP - 156
EP - 171
JO - International Journal of Hyperthermia
JF - International Journal of Hyperthermia
IS - 2
ER -