Investigations into Thermally Mediated Drug Delivery Using a Preclinical System for MRI‐Guided Focused Ultrasound

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 ultrasound (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.