Large-Volume Hyperthermia for Safe and Cost-Effective Targeted Drug Delivery Using a Clinical Ultrasound-Guided Focused Ultrasound Device

Abstract Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation these approaches for drug delivery is challenging, not least because the significant cost overhead MR guidance and much larger volumes need be heated clinically. Using an ultrasound-guided extracorporeal FUS device (Chongqing HAIFU, JC200) with thermistors in a non-perfused ex vivo bovine liver tissue model ribs, we present optimised strategy rapidly inducing (5–15 min) sustaining (>30 (?T <+4°C) large (?92 cm3). We describe successful first-in-human trial targeted LTSLs (TARDOX: phase I study investigate from thermosensitive tumours), which tumour resulted localised chemo-ablation. The heating potentially applicable other indications devices.