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磁共振成像在高强度聚焦超声介导热敏脂质体药物传递中的应用:一项体内概念验证研究。

Magnetic resonance imaging of high intensity focused ultrasound mediated drug delivery from temperature-sensitive liposomes: an in vivo proof-of-concept study.

机构信息

Eindhoven University of Technology, Dept. of Biomedical NMR, Eindhoven, The Netherlands.

出版信息

J Control Release. 2011 Feb 28;150(1):102-10. doi: 10.1016/j.jconrel.2010.10.036. Epub 2010 Nov 6.

DOI:10.1016/j.jconrel.2010.10.036
PMID:21059375
Abstract

Temperature-sensitive liposomes (TSLs) co-encapsulating doxorubicin and 250 mM [Gd(HPDO3A)(H₂O)] were evaluated for HIFU-mediated drug delivery under MR image guidance. In vitro studies showed simultaneous and quantitative release of the drug and the MRI contrast agent from the lumen of the TSLs at 42°C, while no leakage was observed over 1 h at 37°C. In a proof-of-concept study, local hyperthermia has been applied for 30 min in 9L rat tumors using a clinical MR-HIFU system. The local temperature-triggered release of [Gd(HPDO3A)(H₂O)] was monitored with interleaved T₁ mapping of the tumor tissue. A good correlation between the ΔR₁, the uptake of doxorubicin and the gadolinium concentration in the tumor was found, implying that the in vivo release of doxorubicin from TSLs can be probed in situ with the longitudinal relaxation time of the co-released MRI contrast agent.

摘要

温度敏感脂质体(TSLs)共包封阿霉素和 250mM [Gd(HPDO3A)(H₂O)],在磁共振成像(MR)引导下用于 HIFU 介导的药物输送。体外研究表明,在 42°C 下,药物和 MRI 对比剂从 TSL 管腔中同时定量释放,而在 37°C 下 1 小时内无泄漏。在概念验证研究中,使用临床磁共振高强度聚焦超声(MR-HIFU)系统在 9L 大鼠肿瘤中局部应用 30 分钟的热疗。通过肿瘤组织的交错 T₁ 映射监测局部温度触发的 [Gd(HPDO3A)(H₂O)] 释放。发现 ΔR₁、阿霉素摄取和肿瘤中钆浓度之间存在良好的相关性,这意味着可以用共释放的 MRI 对比剂的纵向弛豫时间原位探测 TSL 中阿霉素的体内释放。

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