Ultrasound helps cancer drug cross blood-brain barrier

Meng et al / Science Translational Medicine, 2021

Canadian doctors using ultrasound facilitated the transport of an anticancer drug across the blood-brain barrier in four patients with cerebral metastases. The new method made it possible to double the uptake of the drug by the tumor, and three months after the end of the course of treatment, the tumor size in women decreased by an average of 19 percent. Work published v Science Translational Medicine.

The blood-brain barrier protects the brain from microorganisms circulating in the blood, cytokines, antibodies and white blood cells, which can damage nerve tissue. It allows only nutrients to enter the brain, and this creates problems in the treatment of cancer and neurodegenerative diseases, when doctors need to deliver drugs to the brain. Researchers have been trying to solve this problem for a long time: for example, introduce drugs through the nose to increase their availability. Besides, apply excipients that break the tight contact between endothelial cells and help drugs reach the brain.

Another auxiliary delivery method developed in recent years uses ultrasound to temporarily increase the permeability of the blood-brain barrier. To do this, the patient is injected into the blood with bubbles of a contrast agent, which, under the influence of ultrasound, begin to vibrate, and this opens the gaps between the endothelial cells and allows the drug molecules to pass through them. In animal tests, this method allowed successfully deliver an anti-cancer drug to the brain, in addition, it already confirmed its safety in the first clinical trials. Its effectiveness in clinical trials for the treatment of cancer metastases has not yet been evaluated.

Canadian doctors led by Nir Lipsman from the University of Toronto looked at how effectively trastuzumab (a monoclonal antibody drug) penetrates the brain under the influence of ultrasound. They recruited four women with breast cancer who had brain metastases. The patients underwent six treatment sessions, during which the drug was injected intravenously and the brain was simultaneously exposed to ultrasound. Trastuzumab was labeled with a radioisotope (indium-111) to measure its uptake on computed tomography. In addition, the patients were first treated without the use of ultrasound to measure the baseline brain uptake of labeled trastuzumab.

Ultrasound exposure to the blood-brain barrier increased the tumor uptake of the drug by an average of 101 percent. Three months after the end of the course of treatment, the size of brain metastases decreased by an average of 19 percent. The women tolerated the therapy well, and an additional tomographic study showed that the gaps in the blood-brain barrier closed one day after ultrasound exposure.

Trastuzumab is quite large, which means that most drugs can be delivered to the brain in the same way. This will make it possible to treat not only cancer, but also, for example, neurodegenerative diseases.

Israeli biologists discoveredthat the barrier between blood and brain tissue is not as strong and impervious to large substances as previously thought. It turned out that neuronal stem cells cause the vessel wall to capture and transport substances from the blood.

Anastasia Kuznetsova-Fantoni

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