Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption
Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption
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DOI：
10.1073/pnas.0604318103
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发表时间：
2006-08-01
影响因子：
11.1
通讯作者：
Hynynen, Kullervo
中科院分区：
文献类型：
--
作者：
Kinoshita, Manabu;McDannold, Nathan;Hynynen, Kullervo
基于抗体的抗癌剂是有前途的化学治疗剂。在这些药物中，赫赛汀（曲妥珠单抗），一种人源化抗人表皮生长因子受体2（HER 2/c-erbB 2）单克隆抗体，已成功用于乳腺癌患者。然而，在患有脑转移的患者中，血脑屏障限制了其使用，并且需要不同的递送方法来治疗这些患者。在这里，我们报告，赫赛汀可以通过使用MRI引导的聚焦超声血脑屏障破坏技术的图像引导下，通过血脑屏障局部和非侵入性地进入小鼠中枢神经系统。递送至靶组织的赫赛汀的量与MRI监测的屏障打开的程度相关，使得可以间接估计递送的赫赛汀的量。可归因于该手术的组织学变化极小。这种方法可能代表了一种强大的技术，用于递送大分子试剂，如抗体，以治疗患有中枢神经系统疾病的患者。
Antibody-based anticancer agents are promising chemotherapeutic agents. Among these agents, Herceptin (trastuzumab), a humanized anti-human epidermal growth factor receptor 2 (HER2/c-erbB2) monoclonal antibody, has been used successfully in patients with breast cancer. However, in patients with brain metastasis, the blood-brain barrier limits its use, and a different delivery method is needed to treat these patients. Here, we report that Herceptin can be delivered locally and noninvasively into the mouse central nervous system through the blood-brain barrier under image guidance by using an MRI-guided focused ultrasound blood-brain barrier disruption technique. The amount of Herceptin delivered to the target tissue was correlated with the extent of the MRI-monitored barrier opening, making it possible to estimate indirectly the amount of Herceptin delivered. Histological changes attributable to this procedure were minimal. This method may represent a powerful technique for the delivery of macromolecular agents such as antibodies to treat patients with diseases of the central nervous system.