MRgFUS-Mediated Antibody Delivery Improves Drug Uptake across the BBB

The blood–brain barrier (BBB) is a major obstacle to the delivery of therapeutics to the brain. Magnetic resonance–guided focused ultrasound (MRgFUS) is a technology developed to get around this limitation, providing a noninvasive and spatially precise way of increasing drug delivery across the BBB. It provides a temporary window of access that resolves in 24 hours and has demonstrated promise in preclinical models, but its successful use in humans has yet to be shown. Meng and colleagues used this technique along with the existing regimen for delivery of trastuzumab to four patients with HER2-positive breast cancer and brain metastases. Outpatient procedures of 20 treatments were administered with safety as the primary outcome. No serious adverse events were noted, and patients were generally released from the hospital 2 hours after treatment. Evaluation of efficacy using a radiotracer indicated that MRgFUS-treated lesions increased binding and uptake over control lesions. Furthermore, tumors were either decreased in size or stable as compared to baseline as indicated by a follow-up MRI, with three of the four patients observed showing a decrease in unidimensional tumor measurements after several months. This technique shows multiple advantages over other brain drug delivery approaches, including spatial and temporal control allowing for the specific targeting of regions of the brain that typically are not easily accessed by radiation or surgery and an ability to be combined with other anticancer therapies. This study presents first-in-human evidence of antibody delivery across the BBB using MRgFUS and implicates the use of this technology in the future treatment of other neuro-oncological and neurologic disorders.

Meng Y, Reilly RM, Pezo RC, Trudeau M, Sahgal A, Singnurkar A, et al. MR-guided focused ultrasound enhances delivery of trastuzumab to Her2-positive brain metastases. Sci Transl Med 2021;13:eabj4011.

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