Localised drug release using MRI-controlled focused ultrasound hyperthermia

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 degrees A degrees 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 degrees A degrees C, 41.0 degrees A degrees C and 44.8 degrees A degrees 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.