Seeing disease’s acidic side

Method may allow early detection of tumors by pH

Thanks to a new technique that enables scientists to detect a slight change in acidity, hard-to-find, small tumors may one day be caught earlier. By visualizing pH, the method can map out diseased tissue in mice, a team reported online and in the June 12 Nature.

TELL-TALE SIGN This MRI image of mouse tissue shows that the area with the tumor (in the white circle) is more acidic than the surrounding tissue. Ferdia A. Gallagher, Nature

Researchers say the noninvasive, nontoxic and precise technique has potential to provide an early warning system for cancer and other diseases in people.

“Low pH is associated with many disease states, not just cancer, so the potential for this technique to be a general diagnostic test of malady could be huge,” says Sam Day, a biochemist at the Laboratory of Functional and Molecular Imaging at the National Institutes of Health in Bethesda, Md.

Scientists have long known that pH, a scaled measure of acidity and alkalinity, is thrown off by cancer, inflammation, renal disease and some forms of heart disease, among others. Tumors, for example, are more acidic than the surrounding healthy tissue. What researchers didn’t know was how to pinpoint where slight changes in pH occurred in the body in a safe and reliable manner.

Day and his colleagues created an anatomical map of tissue pH in tumor-ridden mice using an MRI scanner to detect labeled molecules that had been injected. The labeled molecules are nontoxic, enriched versions of bicarbonate — a compound the body makes naturally to balance acidity and maintain its near-neutral pH levels. People already ingest enriched bicarbonate when they take antacids, so it’s unlikely that injecting the bicarbonate will pose a risk, explains Kevin Brindle, a member of the team and a biochemist at the University of Cambridge in England.

Related techniques tested in mice over the last few years also measure tissue pH with MRI scans, but “those are based on non-FDA–approved chemical compounds that are not especially nice things to inject into a person,” says Day. “Also the reading you get from those other methods can be less reliable.”

Accurate measurements of acid-to-alkaline ratios rely on contrast. If the signal radiating from acidic tissue is too dull, it can’t be distinguished from a normal, more alkaline (or basic) background. The team amplified the bicarbonate signal using a “hyperpolarization” technique previously shown to radically increase the signal of other molecules. Hyperpolarization made the bicarbonate signal more than 10,000 times stronger, says Brindle, “Really, it’s huge.”

In theory, the technique could be used to detect and monitor any disease associated with a change in tissue pH. “Instead of waiting weeks or months to see if a tumor shrunk, you could see a response almost instantaneously,” says Jonathan A. Murray. As a general manager at GE Healthcare in Waukesha, Wis., Murray oversees the development of technology to diagnose and treat cancer, heart disease and other conditions. Though he was not involved with this project, he was aware of it. “There will be a whole frontier of hyperpolarizing important chemicals that the body processes to give us insight into disease,” he predicts.

One aspect of the procedure could be tricky when scaled up from mice to humans, says Brindle. “We have to do the whole experiment within two minutes,” he says. After the bicarbonate label is hyperpolarized, the researchers must immediately inject and image the molecule with the MRI scanner. “That’s a challenge,” he admits, “but we are optimistic that it can be done clinically.”

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