Details

Autor(en) / Beteiligte

• Kinoshita, Manabu
• McDannold, Nathan
• Jolesz, Ferenc A.
• Hynynen, Kullervo

Titel

Noninvasive Localized Delivery of Herceptin to the Mouse Brain by MRI-Guided Focused Ultrasound-Induced Blood-Brain Barrier Disruption

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2006-08, Vol.103 (31), p.11719-11723

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2006

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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.