Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood–brain barrier disruption

TLDR

Antibody‑based anticancer agents, such as the HER2‑targeting monoclonal antibody Herceptin, have shown therapeutic success in breast cancer. The study seeks to deliver Herceptin locally and noninvasively into the mouse central nervous system across the blood–brain barrier using MRI‑guided focused ultrasound. MRI‑guided focused ultrasound is employed to disrupt the blood–brain barrier, enabling local, noninvasive delivery of Herceptin into the mouse CNS. Herceptin delivery correlated with the extent of MRI‑monitored barrier opening, caused minimal histological changes, and suggests a powerful technique for delivering macromolecular agents to treat central nervous system diseases.

Abstract

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.