Will cancer spread? Sound out NMR.

Will cancer spread? Sound out NMR 

A Canadian scientist has adapted a standard chemical assaying technique to identify whether solid cancerous tumors have the ability to spawn secondary growths, called metastases. In a recenlty completed study of 200 human adenocarcinomas -- 70 percent colon cancers, 30 percent breast tumors -- Ian C.P. Smith correctly diagnosed 27 cancers as having apparently "no metastatic potential." It is significant, he notes, that none of his diagnoses falsely predicted that a cancer would not spread.

If such metastatic diagnoses prove as reliable as the preliminary studies suggest, they might one day offer physicians the option of prescribing postsurgical radiation or chemotherapy directed only at the primary tumor, says Smith, director of the Canadian National Research Council's Division of Biological Sciences in Ottawa. Thus some patients might qualify for a more benign therapy than the treatment used to tackle unseen metastases today, he says.

Over the past decade, most major hospitals have adopted nuclear magnetic resonance (NMR) imaging, also known as magnetic resonance imaging, as a noninvasive tool for peering into the body. But chemists have used NMR spectroscopy -- which can identify and quantify chemical species within complex samples -- for at least 30 years. And a technique based on this spectroscopic side of the technology lies behind Smith's work, which he described in Toronto last week at the Third Chemical Congress of North America.

Smith irradiated samples (from tumors removed during surgery) with radiofrequency radiation. This energy "excited" nuclei of certain atoms in the cancerous tissue to a higher energy. When the NMR beam shut off, the atoms "relaxed" to their initial energy state. Each chemical constituent has a unique relaxation profile, or signature, that allows its identification.

Smith focused on relaxation rates for the methylene (CH.sub.2.) component of fat, because an Australian study in rats had suggested its association with metastasis. None of the 27 patients whose tumors' methylene spectra relaxed quickly -- usually in abotu 154 milliseconds -- had metastases at the time of surgery or in the two to three years they have been followed since then. However, Smith found, among those patients whose tumor spectra had relaxation times above 350 milliseconds, many had metastases at surgery. Moreover, among the initially metastases-free patients with tumors showing slowly relaxing methylene spectra, "a number have since developed metastases," Smith says.

He also reports that the width of the CH.sub.2. spectral peak -- at least in the colon tumors -- appears to correlate with the tumor's invasiveness. "The narrower it is," he says, "the further the tumor has [invaded] the wall of the colon."

"What I think we are seeing is a unique cancer-cell antigen," Smith says -- a sort of identity marker on the outside of cancer cells that "gives us the slow [NMR relaxation] response." Because this particular signature may be specific to the class of tumors he studies, it cannot yet be extrapolated to solid tumors in general. But if type-specific signatures do occur, Smith says, spectroscopists might be able to read such signatures noninvasively before patients undergo surgery -- learning not only what type of cancer they have but also whether it has spread.

Several researchers, including Smith, have experimentally used NMR spectroscopy to screen blood for signs a patient has cancer. However, Smith found, unusual fat ratios in the blood -- which can be caused by diabetes, heart disease or even pregnancy -- may yield a false indication of cancer. Where NMR monitoring of blood might be useful, Smith says, is in following high-risk persons, like those who have had cancer surgery, to look for early signs of recurring disease.