Agent Approved for Finding Cancer Lymph Nodes

The FDA this month approved the first new agent in over 30 years for finding tumor lymph nodes. Lymphoseek (Technetium Tc99m Tilmanocept), made by Navidea Biopharmaceuticals of Dublin, OH, has been approved for use in patients with melanoma or breast cancer.

Lymphatic mapping is standard for many patients whose tumors are close enough to the skin to be injected with a blue dye or a sulfur-based radioactive tracer. The tracer drains into any lymph nodes that are connected to the tumor. These “sentinel” lymph nodes are then located by eye or by a radiation detector and removed during tumor resection. If a pathologist finds cancer cells in the sentinel lymph nodes, doctors use that information to inform their choice of therapies.

Conventional agents for lymph node mapping do not have any element that targets lymphatic cells—they accumulate passively. In contrast, Lymphoseek is made up of a lymphatic-cell-targeting carbohydrate core attached to a radioactive tracer.

Clinical trials of Lymphoseek have compared the agent with the vital blue dye Lymphazurin (isosulfan blue) in 332 patients and shown no harmful side effects.

Lymphoseek was detected in some lymph nodes not detected by vital blue dye, and in some of those lymph nodes pathology revealed cancer cells.

Vernon Sondak, MD, chair of cutaneous oncology at the Moffitt Cancer Center in Tampa, FL, says this is not surprising, because the radiation detector is more sensitive than the naked eye.

Sondak, who led the trials in melanoma, says it's exciting that an agent designed to target lymphatic cells has been approved. However, he says it's impossible to say whether Lymphoseek outperforms conventional radiotracers without a clinical trial comparing the two, and no such trials are currently planned. Absent that kind of comparison, he expects costs will be key in determining whether surgeons adopt Lymphoseek.

In the future, Sondak and others hope to go beyond simply finding out which are the sentinel lymph nodes and then removing them—with other agents that are being developed with the goal of identifying lymph nodes containing cancerous cells.

Additionally, Sondak says, while lymphatic mapping does help melanoma and breast cancer patients, it is not possible for patients whose tumors are deep inside the body.

“What can we do noninvasively that tells us where cancer cells actually hide out?” asks Sondak. Given that there are sometimes just a few cancer cells in a positive node, that's a hard question to answer, he says.

Other researchers are trying to answer that hard question by developing fluorescent imaging agents that specifically target cancer cells, rather than lymphatic ones. This potentially could reveal cancer-positive lymph nodes during surgery, even for deep tumors that are not eligible for lymphatic mapping today.

Eva Sevick-Muraca, PhD, director of the Center for Molecular Imaging at the University of Texas Health Science Center in Houston, notes that almost 20% of cancer survivors encounter lymphedema as a result of lymph node removal and radiation. By sparing cancer-negative lymph nodes, the risk of encountering lymphedema could be reduced, she says.

Sevick-Muraca and colleagues are developing fluorescent imaging agents that target cancer cells in lymph nodes, potentially allowing surgeons to remove only those nodes. One agent has performed well in a mouse model of prostate cancer, they reported in The Prostate in 2011. For tumor-draining lymph nodes that are not deep, such agents could allow non-invasive staging of cancer, she says.