Paint precisely targets tumor cells

Jim Olson leads development of Chlorotoxin:Cy5.5, a molecular beacon that enables surgeons to see cancer cells 500 times better than an MRI

Center News file photo Dr. Jim Olson led the creation of Chlorotoxin:Cy5.5 in his Clinical Research Division lab. When injected into mouse models, the fluorescent paint illuminated brain tumors as small as 1 millimeter in diameter without lighting up the surrounding normal brain tissue.

A tumor paint developed by researchers at the Hutchinson Center and Seattle Children's Hospital Research Institute will help surgeons see where a tumor begins and ends more precisely by illuminating the cancerous cells. The study, published in the July 15 issue of Cancer Research, shows that the tumor paint can help surgeons distinguish between cancer cells and normal brain tissue in the operating room. The paint is a scorpion-derived peptide called chlorotoxin that is linked to the molecular beacon Cy5.5. Until now, there has been no way to allow surgeons to see tumors "live" during surgery.

Chlorotoxin:Cy5.5 is a fluorescent molecular beacon that emits photons in the near infrared spectrum. This illumination gives surgeons a better chance of removing all of the cancerous cells during surgery without injuring surrounding healthy tissue. This is particularly significant in the brain, where approximately 80 percent of malignant cancers recur at the edges of the surgical site. Current technology, such as magnetic-resonance imaging (MRI) can distinguish tumors from healthy tissue only if more than 1 million cancer cells are present. But Cy5.5 can identify tumors with as few as 200 cancer cells, making it 500 times more sensitive than MRI.

"My greatest hope is that tumor paint will fundamentally improve cancer therapy," said senior author Dr. Jim Olson, of the Clinical Research Division and Children's. "By allowing surgeons to see cancer that would be undetectable by other means, we can give our patients better outcomes."

Olson led the team — including neurosurgeons, engineers and biologists — that created Chlorotoxin:Cy5.5 in his laboratory at the Hutchinson Center. When injected, the substance emits a near-infrared light. In mouse models, the team demonstrated that they could light up brain tumors as small as 1 millimeter in diameter without lighting up the surrounding normal brain tissue. In a prostate-cancer model, the paint enabled detection of as few as 200 cancer cells traveling in a mouse lymph channel.

Chlorotoxin:Cy5.5 is applicable to many cancers, but is especially helpful to surgeons operating on brain tumors. Not only would it reveal whether they'd left behind any bits of tumor, it would also help them avoid removing normal tissue.

Olson and his team are preparing the necessary toxicity studies before seeking approval from the U.S. Food and Drug Administration to begin clinical trials. Chlorotoxin:Cy5.5 could be used in operating rooms in as little as 18 months.

[Adapted from a news release from Children's Hospital & Regional Medical Center.]

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