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

摘要

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 deg 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~R, 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 deg C, 41.0 deg C and 44.8 deg C across the 10 mm diameter target, varying +-0.9 deg 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.