March 27, 2006
Nanoparticles Image Sentinel Lymph Nodes
Patients who have breast cancer, melanoma or gastrointestinal cancer typically undergo sentinel lymph node biopsy prior to surgery in order to first determine whether the patient’s cancer has spread beyond its primary site. Several different nanoparticle formulations may be able to provide a fast, sensitive method for assaying lymph nodes by allowing various imaging technologies to spot metastases either without the need for surgical biopsy or during surgery to remove the primary cancer. Now, two reports show that nanoparticle-based imaging agents do indeed promise improved detection of metastases using either magnetic resonance imaging (MRI) or optical imaging.
Writing in the Journal of Controlled Release, Hisataka Kobayashi, M.D., Ph.D., and his colleagues at the National Cancer Institute’s Center for Cancer Research in Bethesda, MD, show that dendrimers labeled with the MRI contrast agent gadolinium provide an excellent view of lymph nodes clogged with metastatic cancer cells. In particular, a so-called sixth-generation dendrimer (G6 dendrimer) provided the earliest and most distinct view of affected lymph nodes. Dendrimers are spherical polymers of well-defined shape and size that researchers have been using to develop novel imaging and therapeutic agents for use by oncologists.
The NCI team carried out this study in order to determine which of the many different available dendrimer-gadolinium constructs might provide the best imaging data in a clinical setting. To conduct this analysis, the investigators prepared dendrimer-gadolinium formulations of different size and chemical composition. They then used these potential MRI contrast agents to spot metastatic lesions in a mouse model of breast cancer metastases, determining that the G6 dendrimer yielded strong MRI signals from affected lymph nodes within 24 to 36 minutes after the contrast agent was injected into the animal’s bloodstream. This particular dendrimer, the researchers noted, has the optimal size that enables it to get into lymph nodes with metastases rapidly and stay there in high enough concentration to produce a boost in the MRI signal.
The investigators also found that very little of the gadolinium-labeled G6 dendrimer ended up any place other than lymph nodes with metastatic lesions. For imaging applications, this characteristic translates into a low background signal — gadolinium-labeled nanoparticles remaining in the bloodstream or deposited in other tissues would generate an MRI signal that could confound a radiologist’s ability to spot affected lymph nodes. But the researchers also note that since the G6 dendrimer effectively targets lymph nodes containing metastases, this nanoparticle could be used to deliver anticancer drugs to malignant cells in lymph nodes.
In a second paper published in the Annals of Surgical Oncology, a research team headed by John Frangioni, M.D., Ph.D., of the Beth Israel Deaconess Medical Center in Boston, MA, showed that fluorescent quantum dots can be used to find lymph nodes containing malignant cells that have metastasized from tumors of the gastrointestinal tract in pigs. The researchers were able to conduct this study thanks to their earlier development of a real-time fluorescence imaging system designed for use with large animals during surgery. (Click here for an abstract of this earlier work.)
The investigators found that quantum dots injected into the abdominal cavity could be seen in real-time during surgery as they became trapped in sentinel lymph nodes with metastatic lesions. The images were easily interpreted by the surgeon even though the gastrointestinal tract moves as a result of natural forces. Affected lymph nodes could be seen within one minute after the quantum dots were injected. The researchers note that the excellent sensitivity they observed in this study — that is, this technique was able to identify lymph nodes containing even small lesions — bodes well for improving the ability of the surgeon to detect all the lymph nodes containing metastases from gastrointestinal tumors, which in turn should improve the prognosis for patients. The investigators also note that they observed no evidence for acute toxicity that might be caused by the quantum dots.
The magnetic resonance imaging work, which was supported by the National Cancer Institute, was detailed in a paper titled, “Delivery of gadolinium-labeled nanoparticles to the sentinel lymph node: Comparison of the sentinel node visualization and estimations of intra-nodal gadolinium concentration by the magnetic resonance imaging.” Investigators from the Johns Hopkins University and the Ohio State University also participated in this study. An abstract of this paper is available through PubMed.
The optical imaging work, which was also supported in part by the National Cancer Institute, was detailed in a paper titled, “Sentinel lymph node mapping of the gastrointestinal tract by using invisible light.” Investigators from the Massachusetts Institute of Technology also participated in this study. An abstract of this paper is available through PubMed.