Lasers Help Breach Blood-Brain Barrier for Chemotherapy

A new study reveals that laser beams can disrupt the blood-brain barrier (BBB) for up to six weeks, modifying its permeability long enough for chemotherapy treatment.

Researchers at Washington University School of Medicine (WUSTL; St. Louis, MO, USA) conducted a study involving 20 patients with probable recurrent glioblastoma to test a novel hyperthemic method designed to induce temporary disruption of the peritumoral BBB as a potential means to enhance drug delivery. The first step involves magnetic resonance imaging (MRI)-guided interstitial thermal therapy to create a 3-millimeter incision in the BBB, through which a neurosurgeon can robotically insert a laser to heat up and kill brain tumor cells.

To determine the degree and timing of peritumoral BBB disruption, dynamic contrast-enhanced brain MRI is used to calculate the vascular transfer constant (Ktrans) as a measure of permeability. The results showed that Ktrans levels in the peritumoral region peaked immediately post laser ablation, followed by a gradual decline over the following four weeks. Serum levels of brain-specific enolase (BSE), which were also measured and used as an independent quantification of BBB disruption, increased shortly after laser ablation, and peaked at 1-3 weeks before decreasing back to baseline by six weeks.

As part of the study, the chemotherapeutic agent doxorubicin was given intravenously to 13 patients in the weeks following the laser surgery. Preliminary data indicated that 12 of the patients showed no evidence of tumor progression during the 10-week time frame of the study. One patient experienced tumor growth before chemotherapy was delivered; the tumor in another patient progressed after chemotherapy was administered. Most patients went home after one to two days, and none experienced severe complications. The study was published on February 24, 2016, in PLOS One.

“The laser treatment kept the blood-brain barrier open for four to six weeks, providing us with a therapeutic window of opportunity to deliver chemotherapy drugs to the patients,” said lead author Professor of neurosurgery Eric Leuthardt, MD. “This is crucial because most chemotherapy drugs can’t get past the protective barrier, greatly limiting treatment options for patients with brain tumors.”

The BBB is comprised of specialized endothelial cells that form the capillary microvasculature of the central nervous system (CNS), and is essential for brain function. It selectively prevents substances from entering the blood and brain, only allowing such essential molecules as amino acids, oxygen, glucose and water through. On the other hand, it also poses the greatest impediment in the treatment of many CNS diseases because it commonly blocks entry of therapeutic compounds.

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