Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption.
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.
Kinoshita
Manabu
M
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
McDannold
Nathan
N
Jolesz
Ferenc A
FA
Hynynen
Kullervo
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000033:anatomy & histology / Q000000981:diagnostic imaging*; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008279:Magnetic Resonance Imaging; D051379:Mice; D000068878:Trastuzumab; D014463:Ultrasonography / Q000295:instrumentation / Q000379:methods
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab