Targeting Cancer
New option for finding, imaging tumors
(Photo: Karl Maasdam)
A new method for locating, imaging and possibly treating tumors is emerging from research in the Oregon State University College of Veterinary Medicine. Working with Gene Tools LLC, an Oregon biotechnology company, scientists have created a molecule that, when injected into the bloodstream, acts like a bloodhound on the trail of a crook by searching out and latching onto tumor cells.
The molecule, known as a peptide, becomes active in the low-pH environment near a tumor cell, changes shape and embeds itself into the cell membrane. Peptides are made of amino acids, the building blocks of proteins. While the method has immediate applications for detecting and defining tumors, it may also deliver other diagnostic and therapeutic agents to growing cancers, providing an alternative to current medical practices.
“Treatment for breast cancer and other cancers often takes what is commonly called the ‘cut, poison and burn’ approach,” says John Mata, assistant professor and lead author on a report in the December 2007 issue of Nanomedicine: Nanotechnology, Biology and Medi-cine. “Patients that are diagnosed with cancer are often treated by combinations of surgery, toxic chemotherapies and radiation.”
Nanotechnology, the use of tiny molecules designed for specific tasks, may provide a less invasive way of fighting cancer in humans and animals, according to Scott Gustafson, a veterinary surgeon and former OSU faculty member, who was a co-investigator on the study.
“Our demonstration of specific delivery of molecules used to diagnose tumors is an important step in the future of medical diagnosis and treatment using nanomedicines,” Gustafson says.
The researchers used a peptide called PAP-1 to target the cancer cells. The compound of 18 amino acids was developed by James Summerton, a former OSU biochemist and founder of Gene Tools LLC of Philomath. The key was designing a peptide that would respond to low pH. Peptides that embed into membranes occur naturally; however, there are few examples in nature of peptides that will change at very narrow pH ranges to do so.
As tumor cells divide, they grow rapidly and use up the available blood supply, creating hypoxia, or a low level of oxygen. They also use more glucose than normal adjacent tissues. These differences can acidify (reduce pH) the space between the cells within the tumor. As the molecules diffuse into the area, the low-pH environment “throws on a chemical switch,” Mata says, directing the peptide to embed into the tumor cells.
Attaching other molecules to the peptide is not just a theory. The researchers have already used a radioactive element, technetium-99, which they bound to the PAP-1 peptide, to illuminate tumors in mice. The technique allowed researchers to visualize the physical move-ment of their nanotech molecules in real-time using gamma scintigraphy. Additional studies demonstrated pH-specific activation using fluorescent probes attached to PAP-1.
Other OSU scientists participating in the project work in OSU’s colleges of veterinary medicine, pharmacy and engineering.
Learn about biomedical research in the OSU College of Veterinary Medicine at oregonstate.edu/vetmed/biomed/biomed.htm.