Medication Via Catheter Directly to Brain Tumor Target

Newswise — In experiments in mice, Johns Hopkins researchers say they have developed a technique that facilitates the precise placement of cancer drugs at their intended targets in the brain. This approach pairs a technique that guides a catheter through the brain’s arteries with positron emission technology (PET) scans to precisely place cancer drugs at their intended targets in the brain. If future studies show this image-guided drug delivery method is safe and effective in humans, the researchers say it could improve outcomes for historically difficult-to-treat and often lethal brain cancers, such as glioblastoma.

The study published May 1 in The Journal of Nuclear Medicine.

“Brain disorders are often much harder to treat than disorders elsewhere in the body, not only because of the hard flat skullbones that encase the brain complicating surgical access, but also because of the blood-brain barrier, the brain’s sophisticated defense system, denying access to toxins and the majority of drugs,” says Miroslaw Janowski, M.D., Ph.D., associate professor of radiology and radiological science at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Institute for Cell Engineering. “Cancer drugs are often administered as pills or intravenous injections, which are easy and comfortable for patients, but only a tiny portion of these drugs reach the brain tumor. Most of it accumulates in other organs, often leading to serious side effects. The intra-arterial approach solves this problem by allowing us to deliver highly concentrated treatments directly and selectively to the tumor,” says Piotr Walczak, M.D., Ph.D., associate professor of radiology and radiological science at the Johns Hopkins University School of Medicine and a co-investigator on this project.

In their experiments, the research team tested whether a technique commonly used to treat strokes where a catheter is guided from an artery in the leg, through the body and into the brain, could be used to improve precision and efficacy of drug delivery.

The researchers chose to first test this intra-arterial technique with bevacizumab, an antibody protein used to treat a variety of human cancers. Similar antibodies are used also in the rapidly blooming field of immunotherapy.

Due to their large size, antibodies cannot easily cross the blood-brain barrier. To circumvent that problem, the researchers used a drug called mannitol, which is commonly used to lower pressure in the brain. Mannitol is a sugar found naturally in fruits and vegetables, and when delivered to arteries in the brain, it causes the cells making up the blood-brain barrier to contract, leaving spaces in between where large molecules can pass through.

The researchers studied this drug delivery method, comparing intra-arterial versus intravenous injection with and without opening of the blood-brain barrier. The group paired these methods with dynamic PET imaging that allowed them to watch the location of the drug during and after the infusion.

PET scans are widely used to diagnose and treat patients suffering from various diseases, such as cancer and Alzheimer’s disease. These scans are performed by injecting generally safe and relatively short-acting radioactive tracers into the body through a vein to track a variety of metabolic activities, including oxygen flow or the breakdown of sugar molecules.

Janowski’s team used one of these tracers, Zirconium 89, to label the bevacizumab antibody.

In the first experiment, the researchers anesthetized four healthy mice and guided a catheter to the brain. The researchers administered...

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