Nanoparticles Aid in Cancer Staging
Iron oxide particles less than 5 nm in diameter may become the contrast agent that enables clinicians to use magnetic resonance imaging (MRI) instead of resection or biopsy to distinguish malignant lymph nodes from those free of tumor cells.
Researchers in the Netherlands and Boston, Massachusetts, recently reported in the New England Journal of Medicine that an MRI contrast agent consisting of highly lymphotropic iron oxide nanoparticles enabled clinicians to detect small nodal metastases that otherwise would have gone undetected in 33 of the 80 patients with prostate cancer.1
Establishing whether a cancer has spread to a patient's lymph nodes is important in determining the disease's stage and the best course of treatment to prolong survival.
More Than Tiny Particles
Nanotechnology may best be known for its construction of electronic circuits and devices from single atoms and molecules, but this science, based on substances a billionth of a meter in size, has potential uses in health care.
J. Malcolm Wilkinson, managing director at Technology for Industry Ltd., a U.K. consultancy that helps companies transfer their technology from the laboratory to the marketplace, recently described several products in development that are based on nanotechnology1:
1. Wilkinson JM. Nanotechnology applications in medicine. Med Device Technol. 2003; 14 (5):29-31.
In cases of prostate cancer, the researchers wrote, men whose disease has spread to nearby lymph nodes must endure androgen-deprivation therapy. Men whose prostate cancer has not spread from the gland can select from three options: have the prostate removed along with the seminal vesicles and ductus deferens, undergo radiotherapy, or defer treatment until symptoms of the cancer appear, an alternative known as watchful waiting.
If a contrast agent could improve MRI nodal scans, then physicians might be able to stage cancers without requiring samples from tissues other than the original site of the cancer, and patients could undergo fewer invasive procedures.
The contrast agent used in the recently reported research was a freeze-dried powder of dextran-coated iron oxide nanoparticles that, after reconstitution with 0.9% sodium chloride injection, was administered by i.v. infusion over 1530 minutes at a dose equivalent to 2.6 mg of iron per kilogram of body weight. Attachment of low-molecular-weight dextran strands to the iron oxide nanoparticles prolongs their circulatory time.
German researchers who have used the contrast agent in patients with head and neck cancer explained that the iron oxide nanoparticles traverse the vascular endothelium, enter the interstitial tissue, and eventually become trapped by normally functioning lymph nodes and inflamed nodes.2 Lymph nodes that have been invaded by metastasis, however, do not function normally, and MRI can detect an abnormal signal intensity from these nodes after administration of the iron oxide nanoparticles.
All 80 patients in the DutchU.S. study underwent MRI before and 24 hours after infusion of the contrast agent. They then underwent open resection, laparoscope-assisted resection, or biopsy guided by computed tomography to provide the lymph node samples for microscopic examination, which established whether metastases were present.
For the scans made before infusion of the contrast agent, the researchers had the image readers use traditional MRI criteria for declaring a lymph node malignant: length greater than 10 mm if the node was elongated or length greater than 8 mm if the node was round.
The image readers, when viewing images taken 24 hours after administration of the contrast agent, correctly identified all patients who had at least one lymph node metastasis. Without the contrast agent, 45% of these patients were identified.
"NanotechnologyWhat it Means for the Life Sciences," a May 2002 report from The Institute of Nanotechnology in Scotland, describes several developments, such as the delivery of gene therapy by "nano-vectors" and the use of internal tissue implants, in which nanotechnology is expected to have important implications for medical science. The report is available at www.nano.org.uk/saxl.pdf.
Use of the contrast agent enabled the image readers to detect 91% of the metastasis-invaded lymph nodes identified by microscopy, 96% of those whose shorter diameter was 510 mm, and 41% of the metastatic nodes whose short-axis diameter was less than 5 mm. Without the contrast agent, the readers found 35% of all the lymph nodes with metastasis but none of those whose shorter diameter was less than 5 mm.
Five patients reported low back pain during the infusion. The pain disappeared when the infusion was temporarily turned off and did not recur when the rest of the dose was given.
According to the manufacturer, Advanced Magnetics Inc., which supplied the contrast agent for the study, FDA issued a letter in June 2000 stating that the diagnostic aid, whose generic name is ferumoxtran-10, would be approved for marketing if the company fulfilled certain conditions. The indication for use would be the "diagnosis of lymph node disease to assist in directing biopsy and surgery and aid in the staging of metastatic lymph node involvement for a variety of cancers, including breast and prostate cancer." A second indicationthe detection, diagnosis, and characterization of benign and malignant lesions of the liver and spleenwas rejected on the basis of the material submitted to FDA in December 1999, the company stated.
The National Cancer Institute provided part of the study's funding.
1. Harisinghani MG, Barentsz J, Hahn PF et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med. 2003; 348:2491-9.
2. Mack MG, Balzer JO, Straub R et al. Superparamagnetic iron oxideenhanced MR imaging of head and neck lymph nodes. Radiology. 2002; 222:239-44.