Scorpion-derived fluorescent probe paints cancerous tissue

A bioluminescent tumor probe promises to give surgeons a glistening intraoperative view of the dividing line between cancerous and normal tissue.

Dr. James M. Olson, an assistant professor of hematology-oncology, and his interdisciplinary team at Children's Hospital and Fred Hutchinson Cancer Research Center in Seattle developed the unique imaging contrast agent by attaching the peptide chlorotoxin to Cy5.5, a fluorescent molecule that emits near-infrared light.

Chlorotoxin, a component of scorpion venom, preferentially binds to cancer cells.

The researchers demonstrated in mice that brain tumors as small as 1 mm in diameter can be illuminated without lighting up surrounding tissue. CTX:Cy5.5-detected tumors involved as few as 2000 cancer cells, compared with the roughly million labeled cells needed for detection with MRI, Olson said. In a prostate cancer model, as few as 200 cancer cells traveling in a mouse lymph channel were visualized.

The study appeared in the July 15 issue of Cancer Research.

The agent's ability to distinguish cancerous cells from healthy anatomy may help surgeons avoid unnecessarily destroying normal tissue when they excise cancerous lesions. Surgical precision is particularly vital in the brain, where about 80% of malignant cancers recur at the surgical margin, he said.

CTX:Cy5.5 shows promise for imaging melanoma and skin, esophageal, cervical, lung, and colon cancers.

The agent's rapid enhancement rate and long dwell times suggest that it can be conveniently applied in clinical practice. CTX:Cy5.5 binds to cancer cells within minutes after injection, but its signal can be detected at the binding sites for 14 days.

"You can imagine somebody would receive the probe and the next day go to their dermatologist and be scanned to find out which moles are potentially precancerous or cancerous," Olson said.

The researchers are now gathering toxicity data to support an FDA application for clinical trials that could begin within 18 months. They are also developing iron oxide-based nanoparticles coated with chlorotoxin for MR imaging.

"My greatest hope is that tumor paint will fundamentally improve cancer therapy," Olson said. "By allowing surgeons to see cancers that would be undetectable by other means, we can give our patients better outcomes."

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