Scorpion toxin illuminates cancer cells

A tumour paint developed by researchers at Seattle Children's Hospital Research Institute and Fred Hutchinson Cancer Research Center will help surgeons see where a tumour begins and ends more precisely by illuminating the cancerous cells.

The study, published in the July 15 issue of Cancer Research, shows that the tumour paint can help surgeons distinguish between cancer cells and normal brain tissue in the operating theatre.

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 tumours "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 per cent of malignant cancers recur at the edges of the surgical site.

Current technology, such as magnetic resonance imaging (MRI), can distinguish tumours from healthy tissue only if more than one million cancer cells are present. But Cy5.5 can identify tumours with as few as 2000 cancer cells, making it 500 times more sensitive than MRI.

"My greatest hope is that tumour paint will fundamentally improve cancer therapy," the paper's senior author, Dr James M. Olson, said. "By allowing surgeons to see cancer that would be undetectable by other means, we can give our patients better outcomes."

Olson led the team that included neurosurgeons, engineers and biologists. The bioconjugate, Chlorotoxin:Cy5.5 which, when injected, emits a near-infrared light, was created in his laboratory at the Hutchinson Center.

In mouse models, the team demonstrated that they could light up brain tumours as small as one millimetre in diameter without lighting up the surrounding normal brain tissue. In a prostate cancer model, as few as 200 cancer cells travelling in a mouse lymph channel could be detected.

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

Chlorotoxin:Cy5.5 activates within hours and it begins binding to cancer cells within minutes. The Chlorotoxin:Cy5.5 signal lasts for 14 days, illuminating cancer cells. Contrast agents currently in use only last for a few minutes.

Tumour painting has been successfully tested in mice and the pilot safety trials are complete. Olson and his team are preparing the necessary toxicity studies before seeking approval from the Food and Drug Administration to begin clinical trials.

Chlorotoxin:Cy5.5 could be used in operating rooms in as little as 18 months. All clinical studies will have consenting adult participants.

Olson and his team believe that Chlorotoxin:Cy5.5 has the potential to be used in the future as a non-invasive screening tool for early detection of skin, cervical, esophageal, colon and lung cancers. It is also useful in identifying positive lymph nodes which could mean a significant advancement for breast, prostate and testicular cancers.

Source: Children's Hospital and Regional Medical Center of Seattle