Imaging Technique Shows Lymph Nodes, Metastases in Breast Cancer

Breast cancer tends to progress to nearby lymph nodes, but surgeons can find it difficult to determine what tissue to remove with the breast tumor and what to leave intact. National Cancer Institute researchers hope to change that.

“Our advance is that we have a non-invasive method that may minimize surgical trauma,” says the team’s leader, Martin Brechbiel, Ph.D. “At the least, surgeons can acquire a set of images and have a feel, a road map if you will, for what they need to do before the [surgical] procedure begins. Ultimately the technology could have the potential to replace surgery, though that’s not proven yet.”

Brechbiel reported the technique, which uses magnetic resonance imaging and a novel MRI agent, for the first time at the 228th national meeting of the American Chemical Society, the world’s largest scientific society. The pharmaceutical chemist is looking to step up from mouse studies to Phase I clinical trials.

One in seven women will develop breast cancer, according to the American Cancer Society’s 2004 report of cancer statistics. Closely tied to deciding the best approach for the tumor’s removal — a lumpectomy is now the most common — is determining whether and how much of neighboring tissue may also contain cancer cells.

That’s a question surgeons can now rarely answer until the patient is on the operating table and they can probe her lymph tissue directly. And although their decision strongly impacts her chances for cancer recovery and survival, even direct inspection can render it less than clear.

Which node is the sentinel, closest in flow from the breast? Which in line after that should be the last to take? “Also, lymphatic vessels are not always easy just to find. They’re not like bone or a major organ,” Brechbiel points out.

The NCI research has the potential not only to reduce doubt but also to remove much of the decision itself from the operating room. Brechbiel proposes, and has the preliminary data to support, an approach that would send the woman first to the MRI center, where a technician would inject the new imaging agent. Its chemical properties would then light up, in real time, the flow of lymph from breast through lymph vessels to nodes under the arm.

“You can actually watch the filling of nodes from the tumor,” Brechbiel says, referring to observations he and his team have made in transgenic mice. “Some will light up very early, others later. And then you can also reconstruct the data into a three-dimensional image, and rotate it for a three-dimensional road map. The surgeon can know how a patient’s lymph tissue is constructed even before surgical intervention begins.”

Brechbiel’s technique could save time on the operating table, inflict less trauma and possibly even diagnose cancerous nodes as well as delineate the local lymph network. “Cancerous cells can block normal filling of the node, and when that happens you can spot the aberration in flow,” he says.

The imaging agent itself is also new. Other MRI compounds are small molecules, but the NCI group instead has developed a series of dendrimer complexes to carry the magnetic signal. Some of these elaborate scaffolds of polymer each hold a remarkable 256 ions of gadolinium, a rare-earth metal and common magnetic signal in MRI. Dendrimers give a stronger signal even when adjusted for their high molecular weight, and a crisper image because their bulkiness keeps them from leaking through vessel walls.

Having taken the work this far, NCI is now looking for an industrial partner to carry it to clinical trials. Meanwhile, a paper on the research has been accepted for publication later this year by the peer-reviewed Journal of the National Cancer Institute.

The American Chemical Society is a nonprofit organization, chartered by the U.S. Congress, with a multidisciplinary membership of more than 159,000 chemists and chemical engineers. It publishes numerous scientific journals and databases, convenes major research conferences and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.

The paper on this research, INOR 347, will be presented at 2:30 p.m., Monday, Aug. 23, 2004, at the Pennsylvania Convention Center, 108B, during the symposium, “The Chemistry of Biological Molecular Imaging.”

Martin Brechbiel, Ph.D., is section chief of the Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch of the National Cancer Institute in Bethesda, Md.