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

Area of Science:

• Oncology
• Biomedical Engineering
• Pharmacology

Background:

• Lyso-thermosensitive liposomes (LTSLs) enable targeted chemotherapy release via mild hyperthermia.
• Magnetic resonance (MR)-guided focused ultrasound (FUS) offers precise hyperthermia but faces clinical translation challenges due to cost and scale.
• Developing efficient, scalable hyperthermia strategies is crucial for advancing LTSL-based drug delivery.

Purpose of the Study:

• To develop and validate an optimized strategy for rapid and sustained induction of mild hyperthermia in large tissue volumes using ultrasound-guided FUS.
• To assess the clinical feasibility of this strategy for targeted drug delivery with LTSLs in a first-in-human trial.

Main Methods:

• Utilized an ultrasound-guided extracorporeal clinical FUS device (JC200) with thermistors in an ex vivo bovine liver model.
• Optimized heating protocols to achieve mild hyperthermia (ΔT <+4°C) in large volumes (≤92 cm³).
• Conducted a first-in-human clinical trial (TARDOX) for targeted drug delivery of LTSLs in liver tumors.

Main Results:

• Successfully induced and sustained mild hyperthermia in large tissue volumes within 5-15 minutes, maintaining it for over 30 minutes.
• Demonstrated successful clinical translation in the TARDOX trial, achieving localized chemo-ablation through targeted tumor hyperthermia.
• The optimized heating strategy proved effective for localized drug release from LTSLs.

Conclusions:

• Ultrasound-guided FUS provides an effective method for generating controlled hyperthermia in large tissue volumes for targeted drug delivery.
• This optimized strategy overcomes limitations of MR-guided FUS, offering a potentially more accessible clinical approach.
• The findings support the application of this hyperthermia technique for LTSL-based cancer therapies, particularly in liver tumors.