In a world-first study, Sunnybrook researchers have demonstrated the safe delivery of a targeted antibody cancer therapy across the blood-brain barrier using MRI-guided focused ultrasound, to reach tumours which spread to the brain from breast cancer.
HER2-positive breast cancer (HER2+) is also known as Metastatic Breast Cancer or Stage IV breast cancer. HER2+ tumours start in the breast and may spread to areas like the bone, liver or other organs, and brain. There is currently no treatment that can completely cure metastatic breast cancer. Treatments for management of the disease include neurosurgery, hormone therapy and chemotherapy, in combination with radiation therapy.
The blood-brain barrier is a protective layer of cells around the brain that prevents compounds circulating in the bloodstream from entering the brain. It also blocks potentially useful medications, antibodies, chemotherapy agents or other treatments for brain conditions.
Sunnybrook researchers have been exploring the use of focused ultrasound, a non-invasive, image-guided surgical technology to temporarily open the blood-brain barrier. It is considered to be scalpel-free, avoiding incisions to the skin. Sunnybrook is a global leader in focused ultrasound research and clinical trials.
Dr. Nir Lipsman, study principal investigator and director of Sunnybrook’s Harquail Centre for Neuromodulation explains how the research team was able to track the delivery of the therapeutic and how the findings of this innovative focused ultrasound study have the potential to change the treatment care path for patients with brain cancer and other neurological conditions in the future.
What was the goal of this study?
Our team is investigating the use of MRI-guided focused ultrasound to open the blood-brain barrier to enhance the delivery of an antibody therapy called trastuzumab to HER2+ breast cancer that spread to the brain.
Trastuzumab is highly effective at controlling breast cancer outside the brain, but very little of it gets inside the brain because of the blood-brain barrier. A safe, reversible means of opening the barrier can potentially deliver trastuzumab to where it’s needed most. Although we’ve always suspected that focused ultrasound can be used to improve drug delivery, this is the first trial that proves this by directly visualizing the drug in the brain.
How did the research team capture images of the antibody therapy crossing the blood-brain barrier?
The procedures are performed inside the MRI, which is used to help target specific areas of the brain where focused ultrasound is directed to temporarily open the blood-brain barrier. Trastuzumab is administered to trial participants during focused ultrasound, while they are inside the scanner.
In past studies, we used gadolinium, an MRI contrast agent, as an indirect measure of blood brain barrier opening. We saw contrast in areas where we opened the barrier and the following day the contrast was gone, an indication that the blood-brain barrier had safely opened and then closed.
In our current study, our team of researchers tagged the antibody therapy with a special compound. This allowed us to track and directly visualize the therapy using single photon emission computerized tomography (SPECT) imaging. This radiopharmaceutical drug was developed by Professor Raymond Reilly and his team at the Leslie Dan Faculty of Pharmacy at the University of Toronto.
In addition to showing the antibody therapy had crossed the blood-brain barrier, the SPECT scan showed it in the brain 48 hours after the procedure, well after the blood-brain barrier had closed. This is the first visual confirmation that focused ultrasound can improve the delivery of targeted antibody therapy across the blood-brain barrier in human cancer patients.
What do the study findings mean for patients?
Although still very early, the findings are promising, and with continued research have implications well beyond cancer to other brain conditions, including Parkinson’s disease and Alzheimer’s, where medications cannot cross the blood-brain barrier due to their size. Use of focused ultrasound can then help temporarily open the blood-brain barrier for better passage.
This is not a cure for HER2+ metastatic breast cancer but it is an early and critical step. With each step, we are finding new ways of potentially making treatment more feasible and tolerable for patients that could one day improve management of tumours and quality of life.
What does this mean for the field of focused ultrasound?
For focused ultrasound, this is a major step forward. We have demonstrated that a large compound can be delivered safely to the brain, beyond the blood-brain barrier, using non-invasive ultrasound. This has long been theorized in the field, but never proven, until now. It’s an exciting development but we are still very much in the early stages of research.
Sunnybrook researchers, from physicists, to engineers, to basic scientists and clinicians, are actively exploring new and less-invasive ways to enhance the delivery of a whole range of therapeutics to the brain and focused ultrasound is a major part of that effort. It’s promising, and as an innovative approach, has the potential to change the way we treat brain conditions for years to come.Watch and learn more about this world-first clinical trial
Learn more about focused ultrasound at Sunnybrook: sunnybrook.ca/focusedultrasound