大脑中的转移性肿瘤现在是癌症死亡的主要原因之一。由于诊断较晚和跨血脑屏障（BBB）的治疗效果不佳，目前的治疗方法基本上无效。研究表明，将磁共振成像 (MRI) 造影剂与 VCAM-1（抗 VCAM1）单克隆抗体结合可以检测微转移，其体积比目前临床可检测到的微转移小两到三个数量级。本研究的目的是利用这种靶向方法，利用功能化微泡和超声波在早期转移部位实现局部和临时的血脑屏障打开。方法：合成了抗 VCAM1 功能化的微泡，并在体外显示其与表达 VCAM-1 的细胞结合。然后在单侧乳腺癌脑转移小鼠模型中进行体内实验，使用钆-DTPA (Gd-DTPA) 增强 MRI 来检测血脑屏障开放。注射 Gd-DTPA 和靶向微泡后，整个脑部同时暴露于超声波（0.5 MHz、10% 占空比、0.7 MPa 峰值负压、2 分钟治疗时间）。然后进行 T1 加权 MRI 以确定 BBB 开口，然后通过免疫球蛋白 G (IgG) 免疫组织化学进行组织学确认。结果：在用靶向微泡和超声治疗的小鼠中，治疗 5 分钟后，与右半球相比，在左肿瘤半球中观察到 Gd-DTPA 和 IgG 的外渗量显着增加。没有观察到急性不良反应。由于研究的性质，没有对长期生物效应进行调查。结论：结果证明了使用靶向微泡与低强度超声相结合将 BBB 开口定位到大脑转移部位的可行性。这种方法在治疗无法用传统成像方法先验确定其位置的转移性肿瘤方面具有潜在的应用。© 作者。

Metastatic tumours in the brain now represent one of the leading causes of death from cancer. Current treatments are largely ineffective owing to the combination of late diagnosis and poor delivery of therapies across the blood-brain barrier (BBB). Conjugating magnetic resonance imaging (MRI) contrast agents with a monoclonal antibody for VCAM-1 (anti-VCAM1) has been shown to enable detection of micrometastases, two to three orders of magnitude smaller in volume than those currently detectable clinically. The aim of this study was to exploit this targeting approach to enable localised and temporary BBB opening at the site of early-stage metastases using functionalised microbubbles and ultrasound. Methods: Microbubbles functionalised with anti-VCAM1 were synthesised and shown to bind to VCAM-1-expressing cells in vitro. Experiments were then conducted in vivo in a unilateral breast cancer brain metastasis mouse model using Gadolinium-DTPA (Gd-DTPA) enhanced MRI to detect BBB opening. Following injection of Gd-DTPA and targeted microbubbles, the whole brain volume was simultaneously exposed to ultrasound (0.5 MHz, 10% duty cycle, 0.7 MPa peak negative pressure, 2 min treatment time). T1-weighted MRI was then performed to identify BBB opening, followed by histological confirmation via immunoglobulin G (IgG) immunohistochemistry. Results: In mice treated with targeted microbubbles and ultrasound, statistically significantly greater extravasation of Gd-DTPA and IgG was observed in the left tumour-bearing hemisphere compared to the right hemisphere 5 min after treatment. No acute adverse effects were observed. There was no investigation of longer term bioeffects owing to the nature of the study. Conclusion: The results demonstrate the feasibility of using targeted microbubbles in combination with low intensity ultrasound to localise opening of the BBB to metastatic sites in the brain. This approach has potential application in the treatment of metastatic tumours whose location cannot be established a priori with conventional imaging methods.© The author(s).