Striking Results Achieved in Lymph System Imaging Using MRI and Nano-Scale Contrast Agent
Determining whether breast cancer has spread to the lymph nodes may become easier to do as well as easier on the patient, based on the results of important new research presented this week at the American Association for Cancer Research (AACR) annual meeting.
Dr. Hisataka Kobayashi, a staff scientist in the National Cancer Institute's (NCI's) Molecular Imaging Program, reported on the development of a new nano-scale contrast agent for use in magnetic resonance imaging (MRI) that provides clear visualization of drainage from a breast tumor to nearby lymph nodes. Use of this new agent, dubbed G6, in two mouse models of breast cancer also allowed Dr. Kobayashi and colleagues from NCI and Johns Hopkins University to clearly visualize whether there were metastases in sentinel lymph nodes - that is, the first lymph nodes to which metastases are most likely to infiltrate - and axillary nodes. The study was conducted at the Metabolism Branch of the NCI Center for Cancer Research.
The finding could be significant because sentinel node biopsy has shown to be just as effective in determining the extent of any metastasis as the more invasive and potentially more damaging option of removing most of the lymph nodes. [Whether sentinel node biopsy increases overall survival compared to full-armpit node dissection has not been shown. Two NCI-sponsored studies, however, are being conducted to answer that very question.]
"With the knowledge of the exact location and extent of tumor infiltration into the lymphatic system, the surgeon can minimize the incision," Dr. Kobayashi explained. If metastasis appears to be contained within the sentinel node, this not only could improve quality of life but also negate the need for further chemotherapy, he added.
In the study, MRI with the G6 contrast agent was compared with MRI using standard contrast agents in normal, transgenic, and xenograft mouse models. MRI using the G6 agent was able to visualize draining lymphatic vessels and sentinel lymph nodes - something that MRI using standard agents did not achieve. In addition, MRI with G6 was able to easily detect a one-millimeter tumor in three-millimeter lymph nodes, a level of precision 100-fold beyond what is possible using conventional imaging methods with other modalities. Finally, MRI with G6 provided images that could allow for differentiation between lymph ducts and nodes and for detection of lymph nodes completely infiltrated by cancerous cells - neither of which is possible using standard agents or other conventional imaging methods.
MRI with the G6 agent works so well, Dr. Kobayashi explained, precisely because of its nano-size, which, at 9 nanometers, is actually more than 10 times larger in diameter than most standard contrast agents. G6 is small enough to quickly get into the lymphatic ducts but still has sufficient stature to ensure that it doesn't leach from the ducts into the capillary vessels.
"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," Dr. 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 humans."