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Injection of hope

Cambridge firm's imaging agent aids in detecting spread of cancer, study says

By Naomi Aoki, Globe Staff, 6/19/2003

iny iron particles developed by Advanced Magnetics Inc. of Cambridge dramatically increase the ability of MRIs to detect whether prostate cancer has spread to other parts of the body, according to a study published in this week's New England Journal of Medicine.

The findings fuel hope for a less invasive and more accurate way to detect the spread of prostate, breast, lung, and colon cancers. The iron particles are an imaging agent called Combidex that is injected into a patient's bloodstream before having an MRI. Combidex has been under review by the Food and Drug Administration for more than three years and is not yet approved.

''If you were to apply this technique across the board in different tumor types, even if the results are not as high as we saw in the study, you'd still be way, way ahead of anything we have out there today,'' said Dr. Mukesh G. Harisinghani, an assistant radiologist at Boston's Massachusetts General Hospital and the lead author of the study.

One in every six men will develop cancer of the prostate, a walnut-sized gland found only in men and located just below the bladder. The second leading cause of cancer death among men in the United States, the disease is expected to kill about 29,000 this year, according to the American Cancer Society. More than 220,000 new cases of prostate cancer will be diagnosed this year.

Currently physicians treat prostate cancer patients by removing lymph nodes near the prostate and testing the nodes for signs of disease. If the nodes are healthy, indicating that the cancer has not spread, surgeons remove the prostate. But if the disease has spread, removing the prostate is not effective, and patients are treated with hormone therapy and radiation, which is often effective in fighting the disease.

The hope is that Combidex would spare patients whose disease has spread from undergoing unnecessary surgeries. Although MRI, or magnetic resonance imaging, technology can be used to detect the spread of cancer, it is not a perfect test.

Shares of Advanced Magnetics began rising this week as news of the New England Journal of Medicine publication leaked out. The company and the journal released the news late yesterday, but an Advanced Magnetics spokeswoman said she believes some subscribers to the journal may have gotten the issue before its official publication date.

''I'm guessing they liked what they read,'' said Advanced Magnetics spokeswoman Lisa Gordon.

If approved by the FDA, Combidex could propel both Advanced Magnetics and Cytogen Corp., the Princeton, N.J., company that will market the product, to profitability. Combidex is expected to cost $100 to $200 per procedure. If it is used in the more than 800,000 MRIs done each year in the United States to detect whether cancers of various types have spread to the lymph nodes, analysts said, the imaging agent could reach sales of as much as $160 million a year.

Even a fraction of that sum would make substantial contributions to both companies' bottom lines, analysts and company executives said. Last year, Cytogen reported sales of nearly $13 million and a loss of $15.7 million. Advanced Magnetics reported $5.7 million in sales and a loss of $1.7 million.

Shares in Advanced Magnetics rose 26 cents yesterday to $6.95. They are up 39 percent since Friday and more than 65 percent this year. Shares in Cytogen rose 20 cents yesterday to $5.81. They have fallen slightly in recent days but are up more than 78 percent this year.

Nonetheless, the question of when and if the FDA will approve the imaging agent remains. Three years ago, the regulatory agency sent Advanced Magnetics an ''approvable'' letter, indicating that Combidex would be officially approved once certain issues were resolved. The company declined to comment on what those issues are or when the imaging agent is likely to be approved.

Some analysts said those issues could be resolved this year. ''It's still before the FDA,'' said Dan DiPietro, an analyst with SCO Financial Group in New York. ''But I think this paper will go a long way to getting this product in the hands of oncologists and radiologists.''

With current technology, lymph nodes appear bright on an MRI, and physicians measure their size to determine whether they are cancerous.

But the study, which included 80 patients from Mass. General and the University Medical Center Nijmegen in the Netherlands, showed that more than 70 percent of lymph nodes contained cancer even though they were not large enough to cause concern on an MRI. Combidex improved the detection of cancerous nodes using MRI technology to 98 percent from 65 percent, according to the study results.

Combidex's tiny iron particles are designed to attach to healthy lymph nodes but not to those containing tumor cells. If the iron particles attach to a lymph node, it appears black on an MRI, making it easily distinguishable from cancerous cells, which are not supposed to be affected by Combidex and therefore should remain bright on the MRI.

Most notably, researchers said, nine out of the 33 patients whose disease had spread would likely have been misdiagnosed by standard procedures. In those patients, the lymph nodes surrounding the prostate, the ones removed and tested during surgical procedures, were healthy because the cancer skipped over them and spread further into the body.

''Once the cancer has spread, it's a totally different ballgame,'' said Dr. Rosaleen B. Parsons, chairman of the department of diagnostic imaging at the Fox Chase Cancer Center. ''Catching these cases could lead to a tremendous difference in the outcome.''

Naomi Aoki can be reached at naoki@globe.com.

This story ran on page E1 of the Boston Globe on 6/19/2003.
© Copyright 2003 Globe Newspaper Company.