Institute of Biomedical Engineering, University of Oxford, Oxford, UK; Nuffield Department of Surgical Sciences, Oxford, UK; Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Institute of Biomedical Engineering, University of Oxford, Oxford, UK.
Ultrasound Med Biol. 2021 Apr;47(4):982-997. doi: 10.1016/j.ultrasmedbio.2020.12.008. Epub 2021 Jan 13.
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 of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically. Using an ultrasound-guided extracorporeal clinical FUS device (Chongqing HAIFU, JC200) with thermistors in a non-perfused ex vivo bovine liver tissue model with ribs, we present an optimised strategy for rapidly inducing (5-15 min) and sustaining (>30 min) mild hyperthermia (ΔT <+4°C) in large tissue volumes (≤92 cm). We describe successful clinical translation in a first-in-human clinical trial of targeted drug delivery of LTSLs (TARDOX: a phase I study to investigate drug release from thermosensitive liposomes in liver tumours), in which targeted tumour hyperthermia resulted in localised chemo-ablation. The heating strategy is potentially applicable to other indications and ultrasound-guided FUS devices.
溶致热敏脂质体（LTSLs）是专门设计的，可在温和的热疗条件下释放化疗药物。临床前研究表明，磁共振（MR）引导的聚焦超声（FUS）系统可以使用实时测温来产生可控制的体积热疗。然而，这些方法在药物输送方面的高通量临床转化具有挑战性，这主要是因为 MR 引导的高成本和临床治疗需要加热的更大体积。我们使用带有热敏电阻的体外临床超声引导 FUS 设备（重庆海扶，JC200），对带有肋骨的非灌注离体牛肝组织模型进行研究，提出了一种优化策略，可以快速诱导（5-15 分钟）和维持（>30 分钟）温和热疗（ΔT <+4°C），适用于大体积组织（≤92 cm）。我们在首例人体临床试验中成功进行了靶向药物输送的溶致热敏脂质体（TARDOX：一项研究在肝肿瘤中热敏脂质体药物释放的 I 期研究）的临床转化，其中靶向肿瘤热疗导致局部化学消融。这种加热策略可能适用于其他适应症和超声引导的 FUS 设备。
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