Lymphatic Drainage Imaging Using A Nano-size Contrast Agent - New Technology

A new advance in nanotechnology will allow physicians to precisely track the early spread of breast cancer cells to surrounding lymph ducts and nodes, helping to better define or even eliminate surgery.

The development is based on nanotech engineering of G6, a contrast agent used in magnetic resonance imaging (MRI), said Hisataka Kobayashi, M.D., Ph.D., staff scientist in the Molecular Imaging Program at the National Cancer Institute of the NIH.

Using G6 as a contrast agent, MRI technology visualizes metastases that have spread to the first and subsequent lymph ducts and nodes, thus defining the extent of surgery needed for the patient.

"In breast cancer patients, the presence of lymph node metastases greatly affects the prognosis, and the degree of surgical intervention needed," said Kobayashi. "If metastases have not advanced beyond the sentinel node, however, there is arguably no need to surgically remove extensive amounts of lymph nodes.

"With the knowledge of the exact location and extent of tumor infiltration in to the lymphatic system, the surgeon can minimize the incision," Kobayashi said. "This method offers hope of improving the quality of life after surgery by limiting the surgery and perhaps negating the need for further painful chemotherapy when metastasis is evident to be contained within the sentinel node and not in downstream lymphatic structures."

The key to maximizing performance of G6 as a contrast reagent resids in the structure of the lymphatic vessels and nodes, Kobayashi said. The molecule needs to be small enough to rapidly enter the lymph ducts in the lymph fluids, yet large enough to remain within the lymphatics and not leech out into capillary vessels. The Johns Hopkins and NCI team tested G6, a dense (240 kDa) molecule with a span of 9 nanometers. The agent was tested using clinically dedicated MRI instrumentation to evaluate clinical setting performance. The performance of G6 was observed in mouse models for breast cancer.

The researchers looked at the rate of flow of G6 through the lymphatics system from the tumor site to determine "ultimate" sentinel nodes and confirmed that those lymph nodes are at greatest risk for initial spread of metastasis of breast cancer cells. Their technology detected 1 millimeter tumors in 3 millimeter lymph nodes, a 100-fold increase in the precision of detecting tumors than possible with existing conventional lymph node imaging technology. The resolution of this imaging technology distinguished both lymph nodes and ducts, which no other currently used method can discern. Furthermore, the technology visualized lymph nodes that had been totally displaced with cancer cells. Previously existing technology is unable to detect nodes fully occupied with cancer cells.

"This method can tell both the location of true sentinel lymph nodes and the presence or absence of metastatic cancer in those nodes within an hour by a single MRI study," Kobayashi said. "We validated the performance of this agent on the clinical machinery in the mouse model, and we expect the drug to perform as well in the human.

"If the drug is approved for human use, we can start clinical trials as soon as the go-ahead is given," Kobayashi said.

Posted 28th March 2004

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